Haematology Flashcards Preview

Year 5: Pathology > Haematology > Flashcards

Flashcards in Haematology Deck (1033)
Loading flashcards...
1
Q

What is Virchow’s triad?

A

Vessel wall, blood, flow

2
Q

What are the consequences of thromboembolism?

A

Death

Recurrence

Thrombophlebitic syndrome

Pul HTN

3
Q

Blood in virchow’s triad

A

Viscosity: Hct, protein/paraprotein

Platelet count

Coagulation system: triggered by TF, generates thrombin, thrombin converts fibrinogen to fibrin (the clot)

4
Q

Draw the blood coagulation pathway

A
5
Q

How is the blood coagulation pathway regulated by thrombin? (draw)

A
6
Q

How is the blood coagulation pathway regulated by Protein C? (draw)

A
7
Q

What are the procoagulant factors?

Anticoagulant factors?

A
8
Q

What is factor 5 Leidin?

A

Factor V Leiden thrombophilia[1] is a genetic disorder of blood clotting. Factor V Leiden is a variant (mutated form) of human factor V (one of several substances that helps blood clot) that causes an increase in blood clotting (hypercoagulability). In this disorder, the Leiden variant of factor V cannot be inactivated by the anticoagulant protein activated protein C, so clotting is encouraged. (With this mutation, the protein secreted that helps blood not clot is unable to do so, and therefore clotting is more likely) [2] Factor V Leiden is the most common hereditary hypercoagulability (prone to clotting) disorderamongst ethnic Europeans

9
Q

What is the most common hereditary cause of hypercoagulability in ethnic Europeans?

A

FVL

10
Q

Vessel wall in Virchow’s triad

A

Expresses anticoagulatn molecules: thrombomodulin, endoethlial protein C R, TF pathway inhibotr, heparans

Does not express TF

Secretes antiplatelet factors: prostacyclin, NO

11
Q

What happens with vessel wall inflammation/injury?

A

Makes the wall prothrombotic

Can be caused by infection, malignancy, vasculitis, trauma

Effects: downregulation of anticoagulant factors (TM), upregulation of adhesion molecules, expression of TF, reduced production of prostacycline

12
Q

What are the implications of thrombosis in Cancer?

A

l In the 12 months after idiopathic thrombosis, approximately 10% of patients will have cancer diagnosed.

lSimple tests, CXR, FBC, CRP, profile, urine will detect ~50% of these.

lMost malignancies presenting with thrombosis have a poor prognosis.

¨RR is ~7 for patients with active cancer

¨~ 20% of all VTE occur in patients with cancer

¨% incidence of VTE in year after cancer diagnosis

NB there is variation with type of cancer and extent of disease

13
Q

Which cancer has largest effect on incidence of VTE?

A

Pancreas

14
Q

How does stasis promote thrombosis?

A

Accumulation of activated factors

Promotes platelet adhesion

Promotes leukocyte adhesion and transmigration

Hypoxia produces inflammatory effect on endothelium

15
Q

What are the causes of blood stasis?

A

Immobility: Sx, paraparesis, travel

Compression: tumour, pregnancy

Viscosity: polycythaemia, paraprotein

Congenital: vascular abnormalities

16
Q

When does the risk of PE after air travel start?

A

3-6h

Greatest >12h

17
Q

Implications of combined thrombotic risks

A

Thrombotic factors often combine to produce thrombosis, can have synergistic effect

Have powerful interactions which are unpredictable

e.g.

Pregnancy, increased VIII, fibrinogen, Decreased protein S, Flow

Malignancy: TF on tumour, inflam, flow

Sx: trauma, inflam, flow

18
Q

What are the principles of managing VTE

A

ST prevention: during periods of high risk

Immediate treatment: preventing extension and embolisation

LT prevention

Anticoagulants

19
Q

Anticoagulant therapy:

High dose?

Low dose?

A

High dose: therapeutic

Low dose: prophylactic

20
Q

What are the traditional/standard anticoagulants?

A

Heparin: unfractioneated/LMWH/Direct acting anti-Xa and anti-IIa: IMMEDIATE

Warfarin: DELAYED

21
Q

Administration of different types of heparin?

What are their actions?

Consequence?

A

Unfractionated: IV

LMWH: sub cut

Pentasacchadie: sub cut

All act by potentiating antithrombin

Provide immediate effect: e.g. for treatment of thrombosis, long term disadvantages include daily injections and risk of osteoporosis

22
Q

Monitoring of heparin therapy?

A

LMWH: reliabl pharmacokinetics so not usually required except in renal failure, extemes of weight or risk, unusual conditions.

Monitor using anti-Xa

Unfractionated heparian: unreliable kinetics

Always moinotr therapeutic levels with APTT or anti-Xa

23
Q

What are the anti-Xa direct acting anticoagulants?

A

Rivaroxaban, apixaban, edoxaban

24
Q

What are the direct acting anti-IIa anticoagulants?

A

Dabigatran

25
Q

What are the properties of the direct acting anticoagulants?

A

Oral

Immediate action peaak within 3-4h

Short t1/2

No monitoring

Limited licensed indications thus far

26
Q

What is the use of Warfarin?

Action?

Therefore

What is the impact?

A

Given orally

Indirect effect by preventing Vit K recycling.

Therefore delayed onset of action

Levels of procoagulants falls: II, VII, IX, X

protein C and protien S (anticoagulant factors) also fall

27
Q

Monitoring of Warfarin?

What are the issues with Warfarin therapy?

Implications in pregnancy?

A

Always essential through measuring INR. Derived from PT

Difficulty as Warfarin has numerous interactions e.g. dietary K, variable absorption, interaction with other drugs

Teratogenic

28
Q

Action of heparin vs warfarin vs doac

A

Cofactor for AT vs Vit K antag vs direct enzyme inhibition

29
Q

Reversal of heparin

warfarin

DOAC?

A

Protamine

Factor concentrate, vit K

none atm

30
Q

Pregnancy: heparin

warfarin

DOAC

A

Heparin: safe

Warfarin: teratogenic

DOAC: no data- avoid

31
Q

Who receives thromboprophylaxis?

A

People at risk: Sx, immobility, pregnancy, general medical inpatients

32
Q

What is used for thromboprophylaxis?

And the features of each Rx?

A

LMWH: daily, e.g. tinzaparine 4500u/ Clexane 40mg

Rivaroxaban

TED stocking for Sx or if heparin contraindicated?

33
Q

Bleeding risk assessment for anticoagulant therapy

Patient factors

A

Patient: bleeding diathesis, platelt count <100, acute CVA in prevous month (eith categrory)

BP >200 / >120

Severe liver disease

severe renal disease

Active bleeding

anticoagulant or antiplatelet therapy

34
Q

Bleeding risk assessment for anticoagulant therapy

Procedure features

A

Neuro, spinal, eye Sx

Other with high bleeding risk

LP, spinal/ epi in previous 4 hours

35
Q

What is essential for treatment of DVT/PE

What is the approach

A

Immediate anticoagulation

LMWH (175u/kg) + Warfarin (some NOACS e.g. rivaroxaban now lciensed). Stop LMWH when INR in therapeutic range

Continue for 3-6m

Patients with cancer continue LMWH not Warfarin

Elasticated stocking for 2y to prevent postphlebitic syndrome

36
Q

Duration of LMWH/Warfarin based on cause

1st VTE, known cause:

A

3m

37
Q

Duration of LMWH/Warfarin based on cause

Cancer

A

LMWH 3-6m

38
Q

Duration of LMWH/Warfarin based on cause

1st VTE unknown cause

A

3-6m Warfarin, potentially lifelong

39
Q

Duration of LMWH/Warfarin based on cause

1st VTE in thrombophilic patient

A

3m Warfarin

?lifelong

40
Q

Duration of LMWH/Warfarin based on cause

Recurrent VTE

A

lifelong Warfarin

41
Q

What may also be indicated following VTE?

A

TEDS to prevent postphlebitic syndrome

42
Q

Use of thrombolysis in VTE

A

Only for life threatening PE or limb threating DVT

Risk fof ICH ~4%

Reduces subsequent post=phlebitic syndrome

43
Q

PE/DVT risk of recurrence

A

Some studies suggest higher risk of recurrence with PE but some not

Generally VTE means increased risk of recurrence

44
Q

Anticoagulation and recurrence after first VTE with minor precipitant (COCP, flights trauma) length of therapy

A

Generally 3m adequate

45
Q

What are the inherited risk factors for VTE?

A

Antithrombin deficiency

Protein C D

Protein S D

Factor V Leiden, resistance to protein C

Prorthrombin

Lupus anticoagulant

Coag excess:

VIII (10%)

11 (2%),

Fibrinogen

46
Q

What is the most common coagulant excess in inherited VTE?

A

Factor VIII (10%)

47
Q

What are the acquired risk factors for VTE?

A

Age, obesity

Previous DVT, PE

Immobilisation

Major Sx, esp ortho. >30mins, plaster cast immobilisation

Long distance travel

Malignancy, esp pacnreas NB 10% idiopathic VTE due to Ca

Pregnancy, COCP, HRT

Antiphospholipid syndrome

Polycythaemia

Thrombocythaemia

48
Q

What is antiphospholipid syndrome?

A

Antiphospholipid syndrome orantiphospholipid antibody syndrome (APS or APLS), or often also Hughes syndrome, is an autoimmune,hypercoagulable state caused by antiphospholipid antibodies. APS provokes blood clots (thrombosis) in both arteries andveins as well as pregnancy-related complications such asmiscarriage, stillbirth, preterm delivery, and severepreeclampsia.

49
Q

Features of Heparin:

MOA

LMWH administration

Unfractionated administration

Antidote

SEs

A

Potentiates antibthrombin III which inactivates thrombin and factors 9, 10, 11

Given SC daily, does not require monitoring except late pregnancy and reanl failure

IV loading dose then infusion, monitor APTT

Antidote: protamine sulphate

Side effects: heparin induced thrombocytopaenia, osteoporosis (both more common with UFH)

50
Q

Indications for target INR of 2.5?

A

1st episode DVT or PE, AF (2-3)

Cardiomyopathy, symptomatic inherited thrombophilia

Mural thrombus

Cardioversion

51
Q

Indications for target INR 3.5?

A

Recurrent DVT or PE, mechanical prosthetic valve (2.5-3.5)

Coronary artery graft thrombosis

Antiphospholipid syndrome

52
Q

Mx of INR 5-8 no bleeding

A

Withold doses, reduce maintenance, restart when INR <5

53
Q

Mx of INR 5-8 minor bleeding

A

Stop warfarin, VIt K slow IV. Restart when INR <5

54
Q

Mx INR >8 no bleed/minor bleed

A

Stop Warfarin

Vit K oral/IV

no bleeding/if risk factors for bleeding

Daily INR monitoring

55
Q

Mx of major bleeding with raised INR including ICH

A

Stop warfarin

Give prothrombin complex concentrate

If unavailable give FFP

Also give Vit K IV

56
Q

What is the relationship between Cancer and anaemia?

Give some examples of anaemia as the manifestation of malignancy

NB

A

Many causes for cancer associated anaemia

Many cases of anaemia are the first presentation of ca:

Fe deficiency

Anaemia of inflammation (chronic disease)

Leucoerythroblastic anaemia

Haemolytic anaemias: autoimmune, microangiopathic

Ca may also cause 2o polycythaemia e.g. RCC and HCC

57
Q

Fe deficiency and cancer

Cause

Laboratory findings

A

Occult blood:

GI cancer: gastric, colonic/rectal

Urinary tract cancers: RCC, bladder

Reduced Ferritin, transferrin saturation

Raised TIBC

Fe deficiency is bleeding until proven otherwise

58
Q

What is leucoerythoblastic anaemia?

Morphological features

A

Red and white cell precursor anaemia (variable degree of anaemia)

Morphological features: teardrop RBCs (+ aniso and poikilocytosis), Nucleated RBCs, immature myeloid cells

59
Q

What does this blood film schow?

A

Leucoerythroblastic film

Tear drop poikilocytes

Nucleated RBC

Myelocyte

60
Q

Outline the principle causes of a leucoerythroblastic film

A
61
Q

What are the features of myelofibrosis?

A

Massive splenomegaly

Dry tap on BM aspirate

62
Q

What are the common laboratory features of haemolytic anaemia of any aetiology?

A

Anaemia (may be compensated)

Reticulocytosis

Raised UNCONJUGATED bilirubin

Raised LDH

Reduced haptoglobins

63
Q

What are the 2 pathogenci groups of haemolytic anaemia

A

Inherited: all due to defects of the red cell

Acquired: defects of the environment in which the red cell finds itself (except Paroxysmal Nocturnal Haemolytic anaemia)

64
Q

What are the three components of of a red cell and how are they affected by iHA

A

Membrane

Spherocytosis, elliptocytosis

Hb:

Structural (SCD)

Quantitative (thallassaemias)

Enzymes:

G6PD

65
Q

What are the only two types of acquired HA

What is the one test that distinguishes between them?

A

Immune

Non-immune

DAT (Coomb’s test)

66
Q

What are the causes of immune HA?

A

Auto-immune: allo-immune/blood transfusion.

Spherocytes, DAT +ve

Associated systemic disorder:

Cancer of the immune system: lymphoma

Disease of hte immune system: SLE

Infection: disturbing the immune system

67
Q

Features of autoimmune haemolysis

Positive DAT means?

A

Anaemia

Reticuloytosis

Raised LDH

Positive DAT

Either idiopathic or there is an underlying lymphoma/CLL/systemic autoimmune disease e.g. SLE

68
Q

What are the two main causes of spherocytes

How can they be distinguished between

A

They are most commonly found in immunologically-mediated hemolytic anemias and in hereditary spherocytosis, but the former would have a positivedirect Coombs test and the latter would not. The misshapen but otherwise healthy red blood cells are mistaken by the spleen for old or damaged red blood cells and it thus constantly breaks them down, causing a cycle whereby the body destroys its own blood supply (auto-hemolysis).

69
Q

What does this blood film show?

A

Spherocytes

70
Q

What are the causes of acquired haemolytic anaemia: Non-Immune

A

Infection: Malaria

Micro-angiopathic HA

Red cell fragments

Low platelets

DIC/bleeding

Underlying adenocarcinoma

71
Q

Features on this film

What does it show?

A

RBC fragments, thrombocytopenia

MAHA

72
Q

Micro-angiopathy in malignancy (pathogenesis)

A

Adenocarcinomas, low grade DIC

Platelet consumption

Fibrin deposition and degradation

Red cell fragmentation

Bleeding

73
Q

Jaundice/Anaemia/Raised LDH

How would you exclude or diagnose?

Lymphoma with liver involvement

A

Bilirubin conjugated/DAT negative/CT scan liver deposits/BM involved-infiltrated

74
Q

Jaundice/Anaemia/Raised LDH

How would you exclude or diagnose?

Lymphoma with nodes compressing the bile duct

A

Bilirubin conjugated/DAT negative/CT scan nodes around porta-hepatis/BM involved-infiltrated

75
Q

Jaundice/Anaemia/Raised LDH

How would you exclude or diagnose?

Lymphoma with auto immune haemolytic anaemia

A

Bilirubin Unconjugated/DAT positive/CT scan no liver deposits

76
Q

What are the causes of true polycythaemia (raised red cell mass)

A

2o (raised EPO/inappropriate): HCC, bronchial Ca, RCC

Polycythaemia vera: clonal myeloproliferative disorder involving acquired mutaitons in JAK2

77
Q

What are the types of WBC and where are they normal?

A

Mature

Phagocytes: granulocytes, monocytes

Immunocytes: lymphocytes

Immature

Normal in BM in an appropriate%, not normal in PB:

Blasts, promyelocytes, myelocytes

78
Q

What does CLL involve?

A

WBC increased mature cells

79
Q
A

CLL: Increased WBC mature cells

80
Q
A

AML: increased immature cells in PB

81
Q

What are the causes of neutrohilia?

A

Corticosteroids

Underlying neoplasia

Tissue inflammation e.g. colitis, pancreatitis

Myeloproliferative/leukaemic disorders

Infection

82
Q

What are the causes of neutrophilia in infection?

A

Localised and systemic infections, acute bacterial, fungal and certain viral

83
Q

What is characteristic of infection with brucella, typhoid and most viruses in terms of FBC

A

Characteristically do not produce a neutrophilia

84
Q

What are the characteristics of a reactive neutrophilia?

A

Presence bands

Toxic granulation

Signs of infection/inflammation

85
Q

What are the characteristics of a malignant neutrophilia

A

Neutrophilia basophilia plus immature cells and splenomegaly suggests myeloproliferative (CML)

86
Q

Features of CML

A

Neutrophilia basophilia plus immature cells myelocytes, and splenomegaly. Suggest a myeloproliferative (CML)

87
Q

Neutropenia plus myeloblasts=?

A

AML

88
Q
A

Reactive neutrophilia

89
Q
A

CML

90
Q

What are the causes of a reactive eosinophilia?

A

Parasitic infestation

Allergic disease e.g. asthma, rheumatoid polyarteritis, pulmonary eosinophilia

Underllying neoplasms esp. Hodgkins, T-cell NHL

Drugs: erythema multiforme

91
Q

What is a malignant cause of eosinophilia

A

Chronic eosinophilic leukaemia

Eosinophils part of the clone

92
Q

FIP1L1-PDGFRa Fusion Gene found in?

A

Chronic eosinophilic leukaemia

93
Q
A

Eosinophilia

94
Q

Causes of monocytosis

A

Rare, seen in certain chronic infections and primary haematological disorders

Infections: TB, brucella, typhoid, vidal: CMV, VZV

Sarcoid

Chronic myelomonocytic leukaemia

95
Q

What are the relevant investigations to interpret a lymphocytosis

A

Clinical: infection or lhymphoma? Lymphadenopathy or splenomegaly?

FBC: degree of lymphocytosis

Microscopy/morpology: mature vs immature

Flow cytometry: lineage- T or B cells. Stage of differentiation

Molecular genetics

96
Q

Causes of reactive lymphocytosis

A

Infection: EBV, CMV, Toxoplasma, Infectious hepatitis, rubella, herpes

Autoimmune

Neoplasia

Sarcoid

97
Q

Lymphocytosis

>3.5x109/l

What could this be?

A
  • EBV viral infection
  • early CLL
98
Q
A

CLL

99
Q
A

ALL

100
Q

What is the principle of flow cytometry

A

Throughout B cell development, cells at differential stages express different surface antibodies.

Flow cytometry separates these cells on the basis of Ab expression

101
Q

What is multiple myeloma?

A

Neoplastic proliferaiton of bone marrow plasma cells associated with a monoloncal protein in serum and or urine

Production of monoclonal Igs: paraprotein

IgG most common.

Middle-aged to elderly

Afrocarribean’s have increased incidence

102
Q

CRAB

A

Clinical features of MM

Calcium high

Renal failure: plus amyloidosis and nephrotic syndrome

Anaemia (and pancytopenia)

Bone pain: osteoporosis, osteolytic lesions, fractures

+ Hyperviscosity syndrome

103
Q

What are the features of symptomatic plasma cell myeloma

A

Monoclonal protein in the serum and or urine

Bone marrow clonal plasma cells or plasmacytoma

CRAB

104
Q

What are the features of asymptomatic/smouldering myeloma

A

Monoclonal protein in serum at myeloma levels (>30g/l)

10% or more clonal plasma cells in BM

No related organ or tissue impairment

105
Q

Px of myeloma

A

3y with conventional CTx

5y with autlogous stem cell transplation (cure)

106
Q

Epidemiology of MM

A

M>F

Black>white

Doesn’t occur in children

70y/o median diagnosis

Increased incidence if first degree relative

107
Q

Ix in MM

A

Dense narrow band on electrophoreisis

Rouleaux on blood film (RBC stacking)
Bence-Jones protein in urine

Raised ESR (+++)

>10% plasma cells in BM

108
Q

Bence-Jones protein

A

MM

109
Q

Staining in MM

A

H&E

Immune-peroxidase stain for CD138

110
Q

Bony features of MM

A

Multiple sjulll lesions

Plasmacytoma: malignant plasma cell tumour growing within soft tissue

Osteopenia and wedge fractures of hte vertebrae

111
Q

Serum protein electrophoresis

A

IgG 52%

IgA 22%

IgM 12

IgE rare

112
Q

What is the staging system for MM?

A

Durie Salmon

113
Q

What are the crtieria for the staging of Duire Salmon

A

Hb

Serum Ca

Bone disease

IgG

IgA

Urine light-chain M-component

Stages 1-3

International staging system (ISS):

B2-microglobulin

Albumin

114
Q

Stage 1 MM

A

>10g/dl

No bone disease

IgG <50

IgA <30

<4mg urine light chain

<3.5B2 microglobulin

>35 albumin

115
Q

Stage 3 MM

A

Hb <8.5

Raised Ca

Multiple lytic lesions in bone

>70g/dl IgG

>50g/l IgA

Urine light chain >12g

Raised B2 microgloublin

Hypoalbuminaemia

116
Q
A

Multiple myeloma

117
Q

What is MGUS?

A

Monoclonal gammaglobinopathy of unkown significance

<10% plasma cells in marrow

<30h/l monoclonal paraprotein

No CRAB

Incidental finding progressing to MM at 1-2%/year

No therapy needed at this stage

Monitor for transformation

118
Q

What is smoldering MM?

A

Monoclonal gammaglobinopathy of unkown significance

>10% plasma cells in marrow

>30h/l monoclonal paraprotein

No CRAB

No therapy needed at this stage

Monitor for transformation

119
Q

What is Waldenstrom’s Macroglobinaemia?

A

Lymphoplasmacytoid Lymphoma (PLL)

Elderly men

Low grade NHL: lymphoplasmacytoid cells produce monoclonal serum IgM that infiltrates the LNs and BM

Weight loss, fatigues, hyperviscosity syndrome

Treatment: plasmapheresis for hyperviscosity

Chlorambuicl, cyclophosphamide

120
Q

What are the features of hyperviscosity syndrome?

A

Visual problems, confusion, CCF, muscle weakeness

121
Q

What are the criteria for plasma cell leukaemia?

A

>2x10^9 plasma cells in peripheral blood

or

>20% of the leukocyte differential count

122
Q

What are the features of systemic amyloidosis?

A

Ig light chains= paraprotein. Deposition of abn proteniacious substance in tissues

Diagnosed via cong-red: APPLE GREEN BIREFRINGENCE

Presents with macroglossia, carpal tunnel syndrome, peripheral neuropathy, RF

Treatment with CTx or auto-SCT

123
Q

Cong red: apple green birefringence

A

Amyloidosis

124
Q

What is MP?

A

6-mercaptopurine

125
Q

What is VAD?

A

Vincristine

Doxorubicin

Dexamethasone

126
Q

What is CTD?

A

Cyclophosphamide

Thalidomide

Dexamethasone

127
Q

What is MPT?

A

Melphalan

Prednisolone

Thalidomide

128
Q

What is the MOA of thalidomide in MM?

A

Immunomodulatory: alters expression of adhesion molecules, reduces TNF alpha and increases IL-10 leading to increased cell-mediated immunity

Inibits angiogenesis and promotes apoptosis of endothelial cells in established angiogenesis

Advantages: oral, synergistic effects in combination therapy. Used for relapsed myeloma

Toxic, dose-limiting

Side effects

129
Q

What are the side effects of thalidomide?

A

Neuropathy

VTE

Somnolence

Consitpation

130
Q

What is the MOA for Bortezomib

A

Inactivates Nf-kB by binding to the beta ring of 20S proteosome

Good activity, high and rapid response

Expensive, toxic

131
Q

What are the toxic effects of Bortezomib?

A

Neuropathy

Systemic toxicity

132
Q

What are some new drugs in the treatment of MM?

A

Thalidomide

Bortezomib

Lenalidomide

133
Q

What is the therapy of choice in MM

A

Alkylating agent +/- prednisolone

Maintenance with IFN alpha

ASCT curative

Bisphosphonates reduce #s and bone pain

134
Q

Treatment of bone disease in MM

A

Hypercalcaemia: IV fluids, steroids, bisphosphonates

Bone pain: pamidronate, zoledronic acid and clodronate.

135
Q

What are the transplant options in MM?

A

Autologous SCT: treatment of choice for most patients. Collect stem cells and give high dose melphalan

Allogenic SCT: decreased deaths due to lower incidence, of infections and interstitial pneumonitis. Consider in patients under 50 with age matched sibling

136
Q

What are the principle causes of mortality in pregnancy?

A

Genital tract sepsis

Eclampsia

VTE

Amniotic fluid embolism

Haemorrhage

Ectopic

137
Q

What are the haematological demands of pregnancy

A

Iron: 300mg for fetus. 500mg for increased maternal cell mass. RDA30mg. WHO recommends 60mg/d

Folate: increased requirement due to growth and cell division. Additional 200mcg/d. WHO recommends 400mcg/d

138
Q

RCOG folate recommendations

A

Before conception and for >12w gestation

400microg/d

139
Q

What are the risks of Fe deficiency in pregnancy

A

IUGR

Prematuiry

PPH

140
Q

What are the blood count changes in pregnancy?

A

Mild anaemia: dilutional effect, red cell mass rises 120-130%, plasma volume rises 150%

Macrocytosis: may be normal or due to folate or B12 deficicency

Thrombocytopenia (<150): can be physiological

141
Q

Causes of thrombocytopenia in pregnancy

A

Physiological (gestational/incidental thrombocytopenia)

Pre-eclampsia

ITP

MAHA

OAll other causes

Increased platelet size

142
Q

Plt <150 in pregnancy

A

Gestational most likely

then ITp

then PE

143
Q

Plt <100 in pregnanc

A

Gestational most likely cause

then pre-ecl

then ITP

144
Q

Plt <70 in pregnancy

A

ITP = Pre-ecl as most likely cause

Then gestational

145
Q

Features of gestational thrombocytopenia

A

10% physiological decrease

Mechanism poorly defined

Either dilutional effect or increased consumption

Platelet count rises 2-5d post-partum

146
Q

What are the plt cut offs for delivery/epidural

A

Delivery 50

Epidural 80

147
Q

What are the features of thrombocytopenia in pre-ecl?

A

50% of pre-eclamptics get therombocytopenia proportional to severity

Due to increased activation and consumption

Associated with coagulation activation. Incipient DIC, normal PT and APTT.

Usually remits following delivery

148
Q

Features of ITP in pregnancy

A

5% of thrombocytopenia in pregnancy. Can precede pregnancy and start early in gestation

149
Q

Treatment of ITP in pregnancy

A

IV Ig

Steroids

Anti-D in Rhesus negative

150
Q

Foetal effects of ITP

A

Unpredictable when <20

Check cord blood daily

151
Q

What is MAHA?

A

Deposition of plt in small BVs.

Thrombocytopenia

Fragmentation and destruction within the vasculature, results in organ damage: Kidney, CNS (placenta)

152
Q

Blood film in MAHA

A

Fragments

Low plt

Polychromasia (increased RBCs)

153
Q

TTP and HUS in pregnancy

A

More common

Not helped by delivery

Usually earlier than HELLP, usually in 2nd trimester

154
Q

What is the net effect of coagulation changes in pregnancy?

A

Procoagulant state:

Increased thrombin generation

Increased fibrin cleavage

Reduced fibrinolysis and interaction with other maternal factors leading to

Increased rate of thrombus

155
Q

PE in pregnanc

A

Risk highest in 40-46w gestation/post-partum then 0-13w

156
Q

Risks in pregnancy for VTE

A

BMI

FH

Bed rest

Pre-ecl

Operative delivery

Previous VTE

Thrombophilia

Age

Parity

Multiple pregnancy

Other medical problems

Hyperemesis gravidarum/dehdration.

OHSS

Unreltaed surgery

157
Q

D-dimer in pregnancy

A

Already elevated

Useless

158
Q

Complications of thrombophilia in pregnancy

A

Associated with impaired placental circulation

Results in:

IUGR, recurrent miscarriage, late foetal loss, placental abruption, severe Pre-ecl

159
Q

Which thrombophilias are associated with pregnancy complications?

A

Antiphospholipid syndrome: recurrent miscarriage and persistent lupus anticoagulant/anticardiolipin Abs

AT PC and PS deficiency

FVL

High protthombin

160
Q

Treatment of APLS

A

Aspirin

Heparin

161
Q

What is the normal blood loss in

SVD

C-sec

A

300-500mL

900-1100mL

162
Q

Def: PPH

A

>500mL after SVD

>1100mL after C-sec

163
Q

DIC syndromes in pregnancy

A

DIC precipitated by amniotic fluid embolism

Placental abruption

Retained dead foetus

Pre-eclampsia

Sepsis

164
Q

Why does DIC occur in amniotic fluid embolism?

A

Due to tissue factor in te amniotic fluid

165
Q

Why is Hbopathy screening performed in pregnancy?

A

To avoid birthds of children with alpha0 thalassamie which die in utero or from hydrops fetalis

166
Q

How is thalassaemia screening stratified?

A

Based on pregnant women FBC indices

FBC indices:

MCH <27: possible thalassameia trait

<25 requires DNA analyiss

Ethnic origin

167
Q

Options if hbopathy identified in pregnancy?

A

Proceed

Prenatal Dx at 10-12 CVS

Amniocentesis

Foetal blood sampling

USS

168
Q

Features of SCA and pregnancy

A

Painful crises become more frequent, anaemia is exaggerated and transfusions are often required

Also associated with:

Increased risks of hospital admission

Post-partum infection

IU foetal death

IUGR

Prematurity

Perinatal mortality

Pyelonephritis

Low birth weight

PROM

Pre term labour

Pre-ecl

169
Q

What immune disorders are significant in pregnancy?

A

HDN Haemolytic disease of newborn

NAITP

170
Q

What is NAITP?

A

Neonatal alloimmune thrombocytopenia: gaining of Abs to platelets from the mother’s circulation

Genetic differences lead to Ag expression on the foetal platelets.

171
Q

Signs and symptoms of anaemia

A

Weakness

Pale

Tired

Cardiac failure

SOB

Orthopnea

PND

Swollen ankles

Lethargic

Decreased exercise times

Syncope

Palpitations

Tachycarida

Koilonychia (Fe def.)

Glossitis (B12 def)

Jaundice (haemolysis)

Pale mucous membranes

Cardiomegaly

CCF

172
Q

Koilonychia in anaemia

A

Fe deficiency

173
Q

Glossitis in anaemia

A

B12 deficiency

174
Q

Jaundice in anaemia

A

Haemolysis

175
Q

Causes of microcytic anaemia

A

Fe deficiency

Anaemia of chronic disease

Thalassaemia

176
Q

Features of reticulotcytosis

A

Normal resposne to anaemia- haemolysis, haemorrhage and haematinics

Absent reticulocytosis if inadequate or bone barrow failure or after acute haemorrhage as takes 6 hours.

Pushes MCV up

177
Q

What does reticulocytosis do to MCV?

A

Pushes t up

178
Q

Features of Fe deficiency

A

Blood film: pencil cells, anisocytosis, poikilocytosis, hypochromic

Low ferritin, low transferrin saturation

Establish source of blood

179
Q

Blood film: pencil cells, anisocytosis, poikilocytosis, hypochromic

A

Fe deficiency

180
Q

Causes of pancytopenia

A

BM failure

Lymphoma/leukaemia

Aplastic anaemia

RTx, CTx

Myelofibrosis

B12/Folate deficiency

181
Q

Ix of pancytopenia

A

Bone marrow aspirate

Blood film

B12 and folate levels

182
Q

Ix of low platelets

A

Coagulation screen

Blood film

BM aspirate

ANA/RAPA/Antiplatelet Ab/HIV test

D-dimer

Fibrinogen

Blood cultures/CSF/MSU

LFTs

183
Q

DIC=

A

Anaemia and thrombocytopenia

184
Q

Mx of DIC

A

Antibiotics

Blood products; RBCs, platelets, croprecipitate, FFP

Regular bloods to assess response to products

185
Q

Auer rod=

A

Accumulation of granules in myeloid cells

AML

186
Q

How is testing of blood performed?

A

Use known anti-A, anti-B and anti-D reagents to test for ABO and RhD group

Positive test causes agglutination. If the RBCs have agglutinated they are seen at the top of the column

187
Q

What are the methods for testing blood type?

A

Column agglutination

Abbreviated testing

Automated blood grouping

Ab screening

188
Q

Abbreviated blood group testing

A

Blood added to card or tube and reacts with rapid reagents

189
Q

Automated blood grouping

A

Bar coded samples with image analysis, quicker to interpret with no manual steps

190
Q

What is the purpose of the antibody screen?

A

Need to identify clinically significant antibodies and transfuse Abs negative for that antigen.

Thisis to prevent delyed haemolytic transfusion reactions.

Can be done using the indirect antiglobulin technique. Test the pateint’s plasma with 2 or 3 RBCs that contain all the important antigens. Screen by incubating pateint’s plasma with screening cells

191
Q

Cross-matching

A

Blood label: donor RBCs labelled with ABO + D type. And other Rh Ags and K

Select blood.

192
Q

What is the IAT?

A

Patient plasma incubated with donor red cells at 37deg for 30-40mins

This will pick up antibody antigen reactions that could cause extravascular haemolysis. Need to add antiglobulin reagenet

193
Q

Immediate spin cross matching

A

Saline, room T, incubate patients plasmawith donor cells for 5 minutes and spin. This will detect ABO incompatibility. IgM anti-A and or IgM anti-B will bind to RBCs, fix complement and cause cell lysis

194
Q

What is electronic crossmatch

A

LIMS automatically determines compataibility without serological testing of donor cells against patient plasma

195
Q

What is MSBOS

A

Negotiations between surgeons and transufion lab for predictable blood loss from surgery

196
Q

Group and Save or Group and Crossmatch

A

Pt details

Indication for transfusion and urgency

Number of RBCs to crossmatch or group and save

Previous transfusions and date

Special requirements: irradiation, CMV negative

Location of patient

Handwrite on blood sample taken.

197
Q

Methods of autologous blood transfusion

A

Pre-operative autologous deposit of blood, shelf life 5w, taken at weekly intervals with Fe supplementation.

Cell salvage: use a machine to suck up blood during surgery. Can’t do this if there is malignant or bacterial contaminant. Used in obstetric and vascular/bloody surgery

198
Q

What is HDN

A

Person may form red cell Ab through blood transufion or if fetal cells enter woman’s circulation during pregnancy or delivery. Some Ags are more likely to form Abs than other

If maternal Ab level is high, it can destroy fetal red cells if they have corresponding red cell Ag. Leads to HDN (fetal anaemia and jaundice)

Only IgG can cross the placenta.

Anti-D often most responsible.

Other Ab= anti-C, anti-K, IgG ABO

199
Q

Rhesus D isoimmunisation

A

1st preg: Rhesus +ve fetus: RhD positive foetal celss cross the placenta causing anti-D Abs to form

2nd pregnancy: Rhesus +ve foetus: moether is sensitised. Maternal anti-D crosses the placenta and coats foetal RhD +ve cells. Leads to their destruction in spleen and liver

200
Q

What are the clinical features of rhesus disease in foetus

A

Foetal anaemia and HDFN: anaemia and high bilirubin.

Bilirubin accumulates after birth as it is no longer removed by the placenta

Hydrops foetalis

Kernicterus can result

201
Q

Features of hydrops fetalis

A

Accumulation of oedema in at least two foetal compartments, can cause spontaneous abortion and heart failure

202
Q

Kernicterus=

A

Bilirubin induced brain dysfunction

203
Q

What are the methods to prevent rhesus disease

A

Prevent sensitisation in the first place

Anti-D antiglobuline

RAADP

204
Q

Prevention of rhesus sensitisation

A

Transfuse RhD negative childbearing females with RhD negative blood.

Give IM injections of anti-D Ig at times when the mother is at risk of fetomaternal bleed

205
Q

What is the timelit for anti-D to be given

A

72h

Doesn’t work if previous sensitisation

206
Q

What are the different doses of anti-D used

A

<20/40: 250IU

>20/40: 500iU, larger doses are needed for larger bleeds to a FMH/Kleihauer test is conducted to determine the size of the bleed

207
Q

Kleihauer-Betke test

A

Blood test used to measure the fetal Hb transferred from fetus to maternal blood stream and determine severity of bleed.

Acid bath removes adult Hb but not fetal Hb. Staining using Shephard’s method appear rose-pink while adult RBC seen as ghosts.

Percentage of fetal to maternal cells calculated

208
Q
A

Kleihauer test, showing fetal red blood cells in rose-pink color, while adult red blood cells are only seen as “ghosts”.

209
Q

Dosing for FMH

A

125iU/mL

210
Q

RAADP

A

Routine antenatal anti-D prophylaxis for women who are rehsus D negative.

1% of pregnancies have no obvious sensitising event.

Routine anti-D prophylaxis is given in 3rd trimester

500iU at 28 and 34w

or 1500iU at 30w.

211
Q

Routine management of Abs in pregnancy

A

Women undergo screen at 11 and 28w to check for RBC Abs

If Abs are present, quantify, check and monitor levels.

High or rising= more likely to affect the foetus

Monitor for HDFN through MCA Doppler USS

Deliver baby early as HDN gets worse in last few weeks fo gestation

212
Q

in utero Mx of HDFN

A

Monitor using doppler USS

Deliver early

Intrauterine transfusions can be given

Monitor babies Hb and bilirubin at delivery and for several days after.

Transfuse to decrease bilirubin and increase Hb

Phototherapy

Subsequent pregnancies are usually worse

213
Q

What other antibodies are implicated in HDN?

A

Anti-C: less severe.

Anti-kell: causes reticulocytopenia in foetus as well as haemolysis

IgG Anti-A and Anti-B Abs from group O mothers can cause mild HDN but not severe and can be treated with phototherapy

214
Q

What is the difference between forawrd and reverse grouping?

A

Øuse known anti-A and anti-B and anti-D reagents against patient’s RBCs = FORWARD GROUP

Øand A and B reagent RBCs against patient’s plasma (contains IgM antibodies) = REVERSE GROUP

215
Q

Indications for use of platelet as transfusion

A

Massive transfusion

Prevent bleeding post chemo

Prevent bleeding post surgery

Platelet dysfunction or immune cause

216
Q

What is an adult treatment dose?

A

One unit of platelets

Raises platelet count by 30-40

217
Q

When is a platelet transfusion contraindicated?

A

Heparin induced TP and TTP

218
Q

Indications for FFP transfusion

A

Massive transfusion

DIC with bleeding

Liver disease + Risk

Not used to reverse warfarin

219
Q

Draw causes of low plt count

A
220
Q

Draw ABO blood groups

A
221
Q

Draw anti-D doses

A
222
Q

What is SHOT?

A

Serious hazards of transfusion

223
Q

TRALI=

A

Transfusion related acute lung injury

224
Q

TACO=

A

Transfusion associated circulatory overload

225
Q

TAD=

A

Transfusion associated dyspnoea

226
Q

PTP=

A

Post-transfusion purpura

227
Q

How can adverse blood transfusion related events be prevented?

A

Bedside check

Use a giving set with a filter in the line

Don’t add drugs to blood

Don’t keep blood out of fridge for >30m without transfusion

Do routine obs during hte transfusion

228
Q

Immediate clinical action in SHOT

Preventative action

A

ABC

Treat symptoms

Check blood components

Inform transfusion department

Take laboratory sampes

Contact local member of tranfusion team

Complete incident form

Take witness statements

Report to SHOT

Root cause analysis

229
Q

Features of acute transfusion reaction

A

May start as rise in temp, pulse or fall in BP

Fever, rigors, flushing, vomiting, dyspnoea, pain at transfusion site, loin and chest pain, urticaria, itching, headache, collapse

230
Q

Treatment of acute transfusion reaction

A

Severe: 2222. Take down components

Replace tranfusion with saline to keep the vein open, ABC, haem input

Mild: medical assistance, administer antihistamine or paracetamol (diuretics if fluid overload). Observe patient.

231
Q

Features of FNHTR

A

During or soon after hte transfusion, rise in temp of 1 degree, chills and rigors

Slow/stop transfusion

Paracetamol

Caused by Abs against WBCs, less common with leukodepletion

232
Q

Features of allergic reaction to blood transfusion

A

Common esp with plasma

Mild urticarial or itchy rash, sometimes with a wheeze. During or after transfusion. Stop or slow transfusion

Antihistamines

Cause: allergen is the donor plasma, so may not recurr dependant on the IgE specificity in the recipient. More common in recipients with hx of atopy

233
Q

What are the most common reactions with RBCs?

A

Febrile

Allergy

Unclassified

Mixed allergic and febrile

Hypotensive

Anaphylactic

234
Q

What are the most common ATR with platelets?

A

Allergic

Febrile

Anaphylactic

Mixed

Unclassified

Hypotensive

235
Q

What are the most common ATRs with plasma?

A

Allergic

Anaphylactic

Febrile

Hypotnesive

Mixed febrile and hypotensive

236
Q

What are the most common ATRs with mixed components?

A

Anaphylactic=allergic

Febrile=hypotensive

Then mixed allergic and febrile

237
Q

Features of Wrong ABO ATR

A

Sings and symptoms of acute intravascular haemolysis: restlessness, chest/loin pain, fever, vomiting, flushing, collapse, Hburia.

Take samples for FBC, biochemistry, coagulation, repeat cross match and DAT.

Causes: failure of bedside check, wrongly labelled x-match sample, lab error

238
Q

Features of anaphylaxis ATR

A

Severe life threatening reaction soon after hte start of the transfusion

Patient will be in hypotensive shock, breathless with wheeze and have laryngeal and facial oedema

Mech: IgE cross linking with mast cells leading to degranulation.

Caused by: previous exposure to Ag and development of an IgE antibodiy. Classically IgA deficiency or IgE Ab is passively transferred by the transfusion

239
Q

What is the differnce between an anaphylactic and an anaphylactoid reaction?

A

Anaphylactic is IgE mediated

240
Q

Features of IgA deficiency

A

Partial or total deficiency where anti-IgA Abs are more likely to develop.

Can be part of CVID and more commonly associated with infection and autoimmunity. Abs develop in response to sensitising event.

At greater risk of allergic transfusion reactions

241
Q

Endogenous infection of blood products

Exogenous infection of blood products

A

Yersinia enterocolitica

Salmonella

E coli

Strep

Staphy

Pseudomonas

Serratia

242
Q

Prevention of bacetial contamination of blood products

A

R/v blood product

Donor questioning

Screening of platelets occurs within 36h of donation and are held for further 6h nefore release

243
Q

What is TRALI

A

Transfusion associated lung injury.

Acute dyspnoea with hypoxia and bilateral pulmonary infiltrates during or within 6h of tranfusion

244
Q

Mechanism of TRALI

A

Donor anti-leucoyte Abs interact with patients WBC Ags which aggregate and stick in pulmonary capillaries

Results in release of neutrophil proteolytic enzymes and toxic oxygen metabolites which cause lung damage

Prevention is through using male donor plasm and avoiding plasma usage e.g. Warfarin reversal is using vit K.

245
Q

What is TACO

A

Transfusion associated circulatory overload

Occuring within 6h of tranfusion:

Acute resp distress

Tachycardia

Raised BP

Acute or worsening pulmonary oedema

Evidence of positive fluid balance

246
Q

Causes of TACO

A

Lack of attention to fluid balance.

Can be due to cardiac/renal failure or hypoabluminaemia.

Over transfusion

247
Q

What is the impact of 1 unit of RBCs on recipient Hb?

A

Increases by 1g/dL

Check Hb after every 2 units

248
Q

What is TAD?

A

Tranfusion associated dyspnoea

Respiratory distress within 24h of transfusion that does not meet the criteria of TRALI or TACO or allergic reaction.

249
Q

What are the Cxs of massive blood transfusions

A

e.g. one blood volume in one day?

Hypothermia

Hyperkalaemia (as stored RBCs leak K)

Hypocalacaemia (as anticoagulant in each bag binds to Ca)

Air embolism

250
Q

What are the features of delayed haemolytic transfusion reactions?

A

Lysis of red cells= raised bilirubin, decreased Hb, increased reticulocytes, Hburia over next few days.

Can occur to Kidd antigens, anti-D, K, Jk

Can cause renal failure

May require further transfusions

Do DAT

251
Q

What are the intravascular symptoms of haemolytic transfusion reactions?

Extravascular?

A

Red/brown plasma and urine

Fall in Hb and jaundice

252
Q

What are some other causes of haemolysis following transfusion?

A

Bacterial contamination

Mechanical damage

Addition of drugs incompatibile with IV fluids

253
Q

What viruses are tested for in donor blood?

A

HBV, HCV, HIV, HTLV but NB window period for infeciton

Syphillis

CMV (removed through leiukodepletion)

Parvovrisu: can affect foetus and patients with haemolytic anaemia

254
Q

What are the features of TA-GvHD

A

Rare but alway fatal.

Donor’s blood contains viable lymphocytes that are not recognised by host immune system in susceptible patients.

Donor lymphocytes recognise the Ags on patients gut, liver, skin, bone marrow and mount an immunological response

Causes severe diarrhoea, liver failure, skin desquamation, bone marrow failure

255
Q

Who is susceptible to TA-GvHD?

A

Very immunosuppressed: SCT patients, CTx durgs e.g. fludarabine, Hodgkin’s foetus. Donor needs to be HLA matched for intrauterine transfusion. (HLA homozygosity)

256
Q

Prevention of TA-GvHD

A

Identify at risk recipients

Irradiate donor blood to leukodeplete

257
Q

Features of PTP

A

Purpura= pin prick red/purple blood spots due to very low platelets or vasculitis

Appears 7-10d post transfusion and can cause life-threatening bleeding.

Affects HPA-1a negative patients

Usually resolves in 1-4w

Sped by IV Ig

Need to be given HPA-1a negative platelets

258
Q

Features of Fe overload in transfusions?

A

Lots of transfusions (>50) over time can lead to an accumulation of Fe.

This can cause organ damage, to hte liver, heart and endocrine system

Prevented through the use of Fe chelators e.g. desferioxamine once Fe >1000g.

Used in thalassaemia where patients have monthly transfusions

259
Q

Draw SHOT: immediate and delayed

A
260
Q

Draw symptoms of ATR

A
261
Q

Draw fever vs allergic ATR

A
262
Q

Def: lymphoma

A

Neoplastic tumour of lymphod tissue

Often found in LNs and BM. May spill into blood

Sometimes found in other lymphoid tssues e.g. spleen, MALT

Rarely found in skin (T-cell), CNS, testes, breast

263
Q

Risk factors for lymphoma

A

No identifiable risk factor in majority of cases

Constant antigenic stimulation, infection and immunosuppression are known to contribute

264
Q

H. pylori and lymphoma

A

Gastric MALT

Lymphoma

265
Q

Sjogren’s and lyomha

A

Parotid lymphoma

266
Q

Coeliac and lymphoma

A

small bowel T cell lymhoma

EATL (enteropathy associated T-cell lymphoma)

267
Q

Viral causes of lyphoma

A

HTLV1

EBV

HIV

268
Q

HTLV1 and lyphoma

A

Infects T cells by vertical/sexual transmission. May develop adults T-cell leukaemia lymphoma

269
Q

EBV and lymphoma

A

EBV infects B lymphocytes. Carrier state regulated by healthy T cells.

Iatrogenic suppression of T cells e.g. transplantation regimens, leads to increased risk

HIV coinfection may also lead to deregulation of EBV infected B cells

270
Q

Why are lymphocytes at risk of malignancy

A

Prolferative rate

Rely on apoptosis: 90% of lymphocytes die, apoptotsis switched off in germinal centre

Mutations: DNA undergoes deliberate mutations to generate Ig and TcR diversity.

271
Q

Mutations and Ig in lymphoma

A

Ig promoter is highly active in B cells, if an intact oncogene is brought close to the Ig promoter, lymphoma may result.

NHL mutations: majority are translocations

272
Q

What is the generative tissue in the lymphoreticular system

A

BM and thymus

273
Q

What is the reactive LR tissue

A

LNs and spleen: develops immune reaction

274
Q

What is the acquired LR tissue?

A

Extranodal lymphoid tissue e.g. skin, stomach, lung, to develop local immune reaction

275
Q

LN features

A

Peripherally B cells

Centrally, T cells

276
Q

Function of the B cell area in the LN

A

Forms a lymphoid follicle.

In the mantle zone there are naive unstimulated B lymphocytes

In the germinal centre, B cells mix with APC to select them and activate them

277
Q

Diagnosis of lymphoma:

Morphology

A

Cytology

Histology

278
Q

Diagnosis of lymphoma:

Immunophenotyping

A

T: CD3 and CD5

B: CD20

Examines cell distribution, loss of surface proteins, abnormal expression of proteins and clonality of B cell

279
Q

Diagnosis of lymphoma:

Molecular pattern

A

FISH: for translocations

PCR

Diagnostic

Prognostic

280
Q

Features of NHL

A

Most common 80-85%

All lymphomas but Hodgkins

>40 subtypes

281
Q

NHL
presentation

A

Varies from subtype to subtype:

Painless lymphadenopathy often multilocular

Compression symptoms

B symptoms

No pain after ETOH

282
Q

No pain after ETOH

A

NHL

283
Q

How can NHL e classified

A

Mature vs immature

Histologically: high grade vs low grade

Lineage: B or T cell

284
Q

Dx of NHL

Staging

A

Tissue biopsy, WHO subtype

CT scan, PET scan (in aggressive lymphomas)

BM biopsy

LP if risk of CNS

285
Q

What are the prognostic markers in NHL

A

LDH and performance status

286
Q

What are the high grade aggressive NHLs?

A

Burkitt’s

T or B cell lymphoblastic leukaemia/lymphoma

Diffuse large B-cell, mantle cell

Treated on acute leukaemia protocols

287
Q

What are the low grade indolent lymphomas?

A

Follicular

marginal zone

Small lymphocytic

MALT

288
Q

Features of Follicular lymphoma

A

B cell

Indolent

Mostly incurable: median survival 12-15y

t14:18 resulting in overexpression of anti-apoptosis protein Bcl-2

“Follicular pattern” “Nodular appearance”

289
Q

t14:18 resulting in overexpression of anti-apoptosis protein Bcl-2

A

Follicular lymphoma

290
Q

“Follicular pattern” “Nodular appearance”

A

Follicular lymphoma

291
Q

Px in follicular lymphoma

A

Indolent but can transform to a high grade lymphoma

292
Q

Mx of follicular lymphoma

A

Watch and wait

Rixucimab CVP

293
Q

CVP

A

Cyclophosphamide

Vincristine

Prednisolone

294
Q

Features of small lymphocytic lymphoma/CLL

A

Middle aged and elderly found in nodes or blood.

Small lymphocytes, naive or post-germinal centre memory B cells.

CD5 or 23

Indolent but can transform to high grade lymphoma

295
Q

Featurs of mantle cell lymphoma

A

Middle-aged, M>F

Aggressive

Disseminated at presentation

Median survival 3-5y

t11:14 translocation.

Cyclin D1 deregulation

Angular nuclei

296
Q

t11:14 translocation.

Cyclin D1 deregulation

A

Mantle cell lymphoma

297
Q

Angular nuclei

A

Mantle cell lymphoma

298
Q

Presentation of MALT

A

May present with dyspepsia or epigastric pain, B symptoms are uncommon

299
Q

Treatment of MALT

A

Microbial dependent: remove antigen with tirple therapy. Can lead to remission in 75%

Microbial independent: CTx

300
Q

Features of MALT

A

Marginal zone NHL found in middle aged.

Chronic antigen syimtulation:

H pylori-> gastric MALT

Djogrens-> Parotid lymphoma

301
Q

What are the types of Burkitt’s

A

Endemic

Sporadic

Immunodeficiency

302
Q

What is the histology in Burkitt’s

A

Starry sky

303
Q

Features of Burkitt’s

A

Very aggressive

Fast growing

t8:14

c-myc overexpression, rapidly responsive to Rx

304
Q

Rx in Brukitt’s

A

CTx: Rituximab + leukaemia protocol or SCT

305
Q

Features of endemic Burkitt’s

A

Most common in equatorial Africa

EBV associated

Characteristic jaw involvement and abdominal masses

306
Q

Features of sporadic Burkitts

A

Found outside Africa

EBV-associated

Jaw less commonly involved

307
Q

Features of immunodeficiency Burkitts

A

Non-EBV associated

HIV/post-transplant patients

308
Q

Features of Diffuse Large B cell lymphoma

A

Middle aged and elderly

Aggressive

Richter’s transformation

Other lymphomas occur secondary to DLBCL

“sheets of large lymphoid cells, germinal centre or post germinal centre B cells”

Germinal centre phenotype is a good prognostic factor

309
Q

“sheets of large lymphoid cells, germinal centre or post germinal centre B cells”

A

DLBC

310
Q

What are the components of the international prognostic indec for lymphoma?

A

Age >60

Serum LDH >normal

Performance status 2-4

Stage III-IV

More than one extranodal site

311
Q

Rx of DLBC

A

Rituximab-CHOP

Auto-SCT for relapse

312
Q

R-CHOP?

A

R- Rituximab: anti CD20 monoclonal antibody anti-B cell

Cyclophosphamide

Adriamycin

Vincristine

Prednisolone

313
Q

MOA Rituximab

A

Anti CD20: anti B cell

314
Q

Features of peripheral T-cell lymphoma

A

Middle aged and elderly

Aggressive

Large T cells with associated reactive cell population, especially eosinophils

315
Q

Large T cells with associated reactive cell population, especially eosinophils

A

Peripheral T cell lymphoma

316
Q

Features of adult T cell leukaemia/lymphoma

A

Carribean and Japan

Associated with HTLV-1 infection

317
Q

Features of EATL

A

Associated with longstanding coeliac

318
Q

Features of cutaenous T cell lymphoma

A

Associated with mycosis fungoides

319
Q

Features of anaplastic large cell lymhpoma

A

Children and young adults

Aggressive

Large epitheloid lymphocytes

t2:5

Alk-1 protein expression (+ve= better Px)

320
Q

Large epitheloid lymphocytes

A

Anaplastic large cell lymphoma

321
Q

t2:5

Alk-1 protein expression (+ve= better Px)

A

Anaplastic large cell lymphoma

322
Q

Reed-sternberg cell=

A

Hodgkins

323
Q

binucleate/multinucleate owl-eyed cell on background of lyphomcytes and reactive cells=

A

Reed-Sternberg= HL

324
Q
A

Reed-Sternberg cell

325
Q

Clinical presentation of HL

A

Asymmetrical painless lymphadenopathy +/- obstructive/mass effect symptoms

Mediastinal mass, cough, respiratory infectoin, SVCO, dysphagia

Constitutional symptoms (incl pruritus)

326
Q

Alcohol induced pain (rarely)

A

HL

327
Q

Pel-Ebstein fever

A

Cyclical 1-2 weekly fever seen in HL

328
Q

Epidemiology of HL

A

M>F

Bimodal age incidence: 20-29 and >60

329
Q

Most common type of HL?

A

Nodular sclerosing, good Px causing peak incidence in young women

330
Q

Ix in HL

A

CT/PET

Tissue dx: LN or BM biopsy, cell stain with CD15 and CD30

Reed-sternberg cell on a background of lymphocytes and reactive cells

331
Q

Features of classical HL

A

Young and middle aged, often involving single LN and supradiaphragmatic

Thought to be germinal/post-germinal centre in origin

EBV and HLA DPB1 associated

Reed-Sternberg and Hodgkins cells

332
Q

Richter’s transformation

A

Richter’s syndrome (RS), also known as Richter’s transformation, is a transformation which occurs in about 5-10% of B cell chronic lymphocytic leukemia (CLL)[1] and hairy cell leukemia into a fast-growing diffuse large B cell lymphoma, a variety of non-Hodgkin lymphoma which is refractory to treatment and carries a bad prognosis.[2]There is also a less common variant in which the CLL changes into a Hodgkin’s lymphoma. Rarely, transformations to a form of myeloid leukemia have been observed. These extraordinarily rare transformations carry a very poor prognosis. [3]Richter’s transformation affects about 5% of CLL patients at some point during their lives.[4]

333
Q

EBV associated and HLA DPB1

A

Classical HL

334
Q

Features of nodular lymphocyte predominant HL (NLPDHL)

A

Isolated lymphadenopathy

Germinal centre B cell

No EBV association

B cell richnodules with scattered L and H cells.

Can transform to high grade B cell lymhpoma

335
Q

Staging of HL

A

1: one LN region (including spleen)
2: >2 LN regions on the same side of the diagram
3: >2 LN regions on different side of the diagram
4: Extranodal sites: BM, liver

A: no constitutional symptoms

B: constitutional symptoms

336
Q

Mx of Hodgkins

A

Combination CTx used in most cases

RTx often used alongside CTx in large areas.

Intensive CTx and autologous SCT: relapsed patients

337
Q

ABVD

A

Used in HL

Adriamycin

Bleomycin

Vinblastine

Decarbazine

Given at 4 weekly intervals

338
Q

What are the issues for treating HL

A

Combination CTx and RTx increases the risk of secondary C

339
Q

Features of Autologous SCT

A

Patients own SCs

Enbales high dose CTx and RTx to eradicate malignant cells

Frozen SCs then reintroduced into ptient

Used in MM and lymhpoma more than leukaemia

No risk of GvHD

340
Q

Features of allogenic SCT

A

HLA-matched donor SCs are harvested

Patients own BM completely eradicated

Donors SCs are introducted

Used more in leukaemia

GvHD, risk of opprotunistic infections, infertility and secondary malignancies

341
Q

Lymphoma tree

A
342
Q

Draw NHL and the LN

A
343
Q

Draw normal haematopoeisis

A
344
Q

Draw the hierarchy of haematological malignancies

A
345
Q

What are the myeloid malignancies?

A

AML (>20%)

Acute promyelocytic (like AML but more mature cells)

Myelodysplasia

Myeloproliferative

CML (mature cells)

346
Q

What are the lymphoid malignancies?

A

Precursor cell: ALL

Mature cell:

CLL

MM

NHL and HL

347
Q

What are type 1 mutations in haematological malignancies

A

Involved in cellular proliferation e.g. RtK

Activation of TK leads to expression in mature cells

RBCs: PCV

Platelets: thrombocytopenia

Granulocytes: CML

348
Q

What is the BCR-ABL mutation seen in?

What type of mutation

A

CML

Type 1

349
Q

What are type 2 mutations?

A

Prevent differentiation

Translocations create fusion genes

350
Q

What is AML-ETO seen in?

What type of mutation?A

A

AML

Type 2

351
Q

What is PML-RARA seen in?

What type of mutation?

A

APML

Type 2

352
Q

What is t9:22

A

Philadelphia chromosome

Seen in CML

353
Q

What is BCR-ABL

A

Fusion gene created in CML. Philadelphia chromosome

354
Q

What is the philadelphia chromosome?

A

Mutation affecting GM-CSF causing proliferation of the granulocytes

Caused by activating tyrosine kinase mutation

Large numbers of differentiated neutrophils are present in the peripheral blood

355
Q

Large numbers of differentiated neutrophils in peripheral blood with an increase in myelocytes and increased platelets

A

CML

356
Q

Epidemiology of CML

A

M:F 1.4:1

40-60y/o

357
Q

Symptoms of CML

A

Weight loss, lethargy, night sweats, splenomegaly, anaemia, bursing, bleeding and gout

Splenomegaly due to infiltration of cords and red pulp by granulocytes, if massive, infarction may occur

358
Q

What are the phases of CML?

A

Bi or triphasic

Chronic phase: 5-6y stabilisation. 80% diagnosed here. <5% of cells in blood are blast cells.

Leucocytosis 500-5000 myeloid cells. Neutrophils and myelocytes no excess of myeloblasts

Bone marrow very hypercellular due to increased numbers of neutrophils and their precurorors

Accelerated phase: 6-12m. 10-19% of peripheral cells are blast cells

Blast crisis: 3-6m surivival. >20% blast cells.

359
Q
A

Leucocytosis with mature myeloid cells

CML

360
Q

Monitoring of CML

A

FBC and leucocyte count

Cytogenetics: philadelphia chromosome. RT-PCR of the ABL-BCR fusion transcript.

Haematological resposne: complete CHR WBC <10

Cytogenetic response: 0% philadelphia positive

Molecular: reduction in BCR-ABL transcripts.

Molecular most sensitive

361
Q

Treament of CML

A

Need to target activated RtK: ABL kinase inhibitor

362
Q

First line Rx in CML

A

RtK: Imatinib

93% survival at 60m

363
Q

Second line Rx in CML

A

RtKI: dasatanib and nilotinib

364
Q

Management of failure in CML

A

Monitor BCR-ABL transcripts, if rising some may respond to 2nd gen.

Failure of TKIs consider allogenic SCT (good survival in CP, extremely poor in blast crisis)

365
Q

Pathogenesis of AML

A

Two hit model

T8:21 mutation resulting in AML-ETO fusion protein.

This is a tumour suprresor known as p14ARF

366
Q

T8:21 mutation

A

AML

367
Q

Management of AML

A

Supportive:red cell transfusions, platelet transfusions. Nurse in isolation, prompt antiboitcs.

368
Q

Dx of AML

A

Morphology

Immunophenotyping: lineage and stage of differentation. Examine expression of antigens on cell surface.

Cytogenetics: chromosomal translocations

Molecular genetics: detection of fusion mRNA

369
Q

Def: Acute Leukaemia

A

A neoplastic condition characterised by rapid onset, early death if untreated, immature blast cells and BM failure

370
Q

What lineage of cells is affected in AML

A

Pluripotenet HSC or granulocyte/monocyte precursor

371
Q

What lineage of cells is affected in CML

A

Pluripotent HSC

372
Q

What lineage of cells is affected in B-ALL

A

B cell

373
Q

What lineage of cells is affected in T-ALL

A

T cells

374
Q

What lineage of cells is affected in CLL

A

Terminal B cell

375
Q

Haematological definition of acute leukaemia

A

Immature blasts >20% BM cells

376
Q

What are the clinical features of acute leukaemia

A

BM function failure: anaemia, thrombocytopenia, neutropenia

Organ infiltration: hepatomegaly, splenomegaly, lymphadenopathy, bone pain, CNS, skin, gum hypertrophy

377
Q

Aetiology of acute leukaemia

A

Uinknown

Ionising radiotherapy

Cytotoxic drugs

Benzene

Pre-leukaemic disordres: myelodsplastic syndrome

DS: AML++

Neonates: often develop transient abnormal myelopoeisis

378
Q

Which population group is affected by ALL?

A

Children

Children get it ALL

379
Q

Which population group is affected by AML

A

Adulthood: risk increases with age

Infants <2

380
Q

What are the clinical features of ALL

A

As for leukaemia but

Lymphadenopathy ++++

CNS involvement ++++

Testicular enlargement

Thymic enlargement

381
Q

What are the clinical features of AML

A

As for leukaemia but

Lymphadenopathy less common.

382
Q

What is acute promyelocytic anaemia?

A

Medical emergency

Prone to DIC

383
Q

Ix in ALL

A

High WCC

Lymphocytes/precursors +++

384
Q

Ix in AML

A

High WCC

Auer rods and granules

Myeloperoxidase and Sudan Black B stains

385
Q

Auer rods

A

AML

386
Q

T15:17 associated with

A

Acute promyelocytic leukaemia. Increased risk of DIC

387
Q

What is classical AML

A

T15:17

388
Q

Clinical features of Acute Monocytic leukaemia

A

CNS disease, skin infiltration, gum infiltration, organomegaly.

389
Q

What is an issue with very high WCC?

A

Hyperviscosity.

390
Q

What has a good prognosis in AML?

A

T15:!7

T 8:21

Intermediate and poor risk have normal/complex karyotypes and other chromosomal abnormalities

391
Q

Treatment of AML

A

Supportive: RBC, platelest, FFP if DIC, antibiotics, long line. Allopurinol, U&Es monitoinrg

CTx:

Danorubicin and cytarabine. Combination therapy, non-overlapping toxicity with synergistic effect. 4-5 courses. remission induced in 2 courses and consolidated in 2-3 courses.

Allo-SCT in young or if poor prognosis.

392
Q

CTx in AML

A

Daunorubicin and cytarabine

4-5 courses

Remission induction in first 2

Consolidation in 2-3 courses

393
Q

When is the Px of ALL worse?

A

With increasing age

394
Q

What are the features of B lineage ALL

A

Starts in bonw marrow, very strong association between genetics and prognosis

Poor prognosis associated with philadelphia chromosome

395
Q

What are the features of T cells lineage ALL

A

Starts in thymus which amy become enlarged.

396
Q

Treatment of ALL

A

(Ph +ve need imatinib)

Systemic chemotherapy and CNS directed therapy

Lasts 2-3 yeasr

Remission induction cycle

Consolidation and CNS therapy: intrathecal Ctx to treat occult CNS disease for 6-8 treatments. If lymphoblasts in CSF then more frequent and intesnive therapy required.

Intensification

Maintenance therapy

Consider allogenic SCT

Supportive:

Blood products, Abx, allopurinol, fluids, electrolytes (to prevent tumour lysis syndrome).

May require leukapharesis if extreme leukocytosis

397
Q

CTx treatment of ALL

A

Systemic CTx and CNS directed therapy lasting 2-3 yeasrs with intrathecal CTx to treat occult CNS disease for 6-8 treatments.

398
Q

Case 1: 5 yr boy. WCC 180 x 109/L, Hb 93 g/L, platelet 43 x 109/L. Thymic mass

A

WCC : diagnosis of leukaemia most likely.
o Low Hb and platelet – bone marrow infiltration.

Thymic mass: infiltration by T lymphoblasts.

399
Q

Pathophysiology of Megaloblastic anaemia

A

DNA cannot be produced fast enought to allow cell division at the right time resulting in larger RBCs e.g. folate and B12 deficiency.

Associated with bone marrow features like meagloblasts, ovalocytes in the peripheral blood and hypersegmented neutrophils

400
Q
A

Megaloblastic anaemia

401
Q

What results in the production of codocytes/target cells?

A

Pathologies of the liber spleen which result in increased red cell membrane

402
Q

What are the mechanisms of macrocytic anaemia

A

Megaloblastic anaemia

Red cell membrane disorders

Alcohol

Rapid cell turnover and reticulocytosis

403
Q

Features of macrocytic anaemia caused by rapid red celll turnober and reticulocytosis

A

Diseases in which there is a high red cell production causes a greater proportion of reticulocytes (which are larger) e.g. COPD: low O2 levels induces production, traumatic loss, rapid haemolysis (G6PDD)

404
Q

Normal RBC lifespan

A

120d

405
Q

What is haemolysis?

A

Shortened red cell survival

406
Q

Draw the classiciation of haemolytic anaemias

A
407
Q

Causes of intravascular haemolysis

A

Malaria

G6PD

Mismatch

Cold Ab haemolytic syndromes

Drugs

MAHA: HUS, TTP, PNH

408
Q

What are the MAHAs?

A

HUS, TTP, PNH

409
Q

What are the extravascular causes of HA?

A

Autoimmune, alloimmune, hereditary and spherocytosis

410
Q

What are the inherited causes of HA?

A

Membrane: cytoskeletal proteins, cation permeability

Red cell metabolism

Hb: thalassaemia, SCD, unstable Hb variants

411
Q

What are the consequences of HA?

A

Anaemia

Erythroid hyperplasia with increased rate of RBC production and reticulocytes

Increased folate demand

Susceptibility to Parvovirus B19

Cholelithiasis: increased risk if inherited with Gilbert

Increased risk of Fe overload and osteoporosis

Fe overload can lead to hepatic siderosis

412
Q

What is hepatic siderosis

A

Hemosiderosis (AmE) or haemosiderosis(BrE) is a form of iron overload disorderresulting in the accumulation ofhemosiderin.

Types include:

Transfusion hemosiderosis[1]

Idiopathic pulmonary hemosiderosis

Transfusional diabetes[2][3]

Hemosiderin deposition in the lungs is often seen after diffuse alveolar hemorrhage, which occurs in diseases such asGoodpasture’s syndrome, granulomatosis with polyangiitis, and idiopathic pulmonary hemosiderosis. Mitral stenosis can also lead to pulmonary hemosiderosis. Hemosiderin collects throughout the body inhemochromatosis. Hemosiderin deposition in the liver is a common feature of hemochromatosis and is the cause of liver failure in the disease. Selective iron deposition in the beta cells of pancreatic islets leads to diabetes[1] [2] due to distribution of transferrin receptor on the beta cells of islets [3] and in the skin leads to hyperpigmentation. Hemosiderin deposition in the brain is seen after bleeds from any source, including chronic subdural hemorrhage, Cerebral arteriovenous malformations,cavernous hemangiomata. Hemosiderin collects in the skin and is slowly removed after bruising; hemosiderin may remain in some conditions such as stasis dermatitis. Hemosiderin in the kidneys has been associated with marked hemolysis and a rare blood disorder called paroxysmal nocturnal hemoglobinuria.

Hemosiderin may deposit in diseases associated with iron overload. These diseases are typically diseases in which chronic blood loss requires frequent blood transfusions, such as sickle cell anemia and thalassemia, though beta thalassemia minor has been associated with hemosiderin deposits in the liver in those with non-alcoholic fatty liver disease independent of any transfusions.[4][5]

413
Q

Consequences of all haemolytic anaemias

A

Rasised (unconjugated) bilirubin

Raised urobilinogen

Raised LDH

Reticuylocytosis (raised MCV and polychromasia)

May have gallstone

414
Q

Consequences of intravascular HA

A

Raised free plasma Hp

Decreased haptoglobins (bind Hb)

Hburia dark red urine

Methaemalbuminaemia (Hb and albumin in blood)

415
Q

Consequences of extravascular HA

A

Splenomegaly

416
Q

Clinical features of HA

A

Pallor, jaundice, splenomegaly, pigmenturia, Fhx

417
Q

What are the inherited membrane defects causing HA

A

Hereditary spherocytosis

Hereditary elliptocytosis

Southe East Asian Ovalocytosis

Hereditray pyropoikilocytosis

418
Q

What is the inheritance pattern of HS?

A

AD

419
Q

What are the features of hereditary spherocytosis

A

Ankyrin or spectrrin deficiency

Mechanical abnromality acoompanied by osmotic changes

Susceptibility to parvovirus B19 and develop gallstones

Extravascular haemolysis: splenomegaly.

Spherocytes, increased osmotic fragility, -ve DAT, flow cytometry

420
Q

Spherocytes, increased osmotic fragility, -ve DAT, flow cytometry

A

Hereditary spherocytosis

421
Q

Why does hereditary spherocytosis cause splenomegaly?

A

Beacuse it is extravascular HA

422
Q

What is the osmotic fragility test

A

Hypotonic saline-> lysis.

423
Q
A

Hereditary spherocytosis

424
Q

Treatment of hereditary spherocytosis

A

Splenectomy

Folic acid

425
Q

What does a negative Coomb’s test tell you?

A

That the HA is not immune mediated

426
Q

What interactions are disrupted in spherocytosis?

A

Vertical interactions.

427
Q

What is the most common cause of hereditary spherocytosis

A

Mutation in Ankyrin

428
Q

What population commonly affected by HS?

A

Hereditary spherocytosis is the most common disorder of the red cell membrane and affects 1 in 2,000 people of Northern European ancestry

429
Q

Minkowski–Chauffard syndrome

A

Hereditary spherocytosis

430
Q

Reduced binding of dye eosin-5-maleimide?

A

Hereditary spherocytosis

431
Q

Inheritance of elliptocytosis

A

AD

432
Q

What is the msot common cause of hereditary ellliptocytosis?

A

Spectrin mutaiton (alpha)

433
Q

What are the features of hereditrary elliptocytosis?

A

Mechanical dysfunction without osmot changes

Severity of disease ranges from hydrops foetalis to asymptomatic

Disruption of horixontal interactions

434
Q

What is the inheritance of hereditary pyropoikilocytosis?

A

AR

435
Q

What are the features of hereditrary pyropoikilocytosis?

A

AR

Abnormal sensitivity to heat causing haemolysis

Considered a special form of elliptocytosis

436
Q
A

Hereditary elliptocytosis

437
Q
A

Hereditary pyropoikilocytosis

438
Q
A

SEA Ovalocytosis

439
Q

What are the features of SEA ovalocytosis?

A

Form of hereditary elliptocytosis most common in Malaysia and papau new guinea.

Confers some protection to M. falciparum

Macro-ovalocytes with one or two slits in 20-50% of the cells.

Heterozygotes asymptomatic, homozygosity presumed lethal

440
Q

What is the commonest RBC enzyme defect?

A

G6PD

441
Q

What are the features of G6PDD

A

Prevalent in areas of malarial endemicity

Most common RBC enzyme defect- X linked.

Attacks: rapid anaemia and jaundice with bite cells and Heinz bodies (blue deposit= oxidised Hb)

442
Q

What is the function of G6PD

A

G6PD catalyses the first step in the pentose phosphate pathway which generates NADPH which is required to maintain intracellular glutathione. GSH is an antioxidant and protexts cellular components

443
Q

What are the clinical effects of G6PDD

A

Neonatal jaundice

Acute haemolysis (triggered by oxidants/infection)

Chronic haemolyic anaemia

444
Q

What is the clinical course of G6pD?

A

Steady state is asymptomatic

Acute haemolysis occurs due to oxidant stress

445
Q

What type of HA is G6PD?

A

Intravascular

446
Q

What factors may precipitate HA attack in G6PD?

A

Drugs:

primaquine (antimalarial), sulphonamides, ciprofloxacin, nitrofurantoin (antibiotics), other drugs: dapsone, Vit K. Broad beans (fava beans), moth balls). Acute stressors e.g. infection

447
Q

Treatment of G6PD

A

Avoid precipitants

Transfuse if severe

Genetic subtypes give chronic haemolysis for which splenectomy is a good treatment

448
Q

Heinz bodies

A

Seen when stained with methylene blue.

Formed by Hb damage by oxidants

G6PD

449
Q

What population commonly affected by G6PDD?

A

African, mediterranean, middle eastern

450
Q

What is the inheritance of pyruvate kinase deficiency?

A

Autosomal recessive but AD has been observed

451
Q

What is pyruvate kinase?

A

Most common enzyme deficiency of the glycolytic pathway.

452
Q

What are the cliniical features of pyruvate kianse deficiency

A

HA of varying severity

Can cause severe neonatal jaundice and splneomegaly

453
Q

Pathophysiological of pyruvate kinase deficiency

A

ATP depltion

Loss of K through lack of ATP impairing Na/K ATPase and loss of H2O

Dehydrated and rigid cells and destruction of poorly deformable cells.

Spleenctomy to treat

454
Q

Mx of HAs?

A

Folic acid supplementaitons

Avodi precipitating factors

RBC transfusion/exchange

Immunisation against BBV

Monitor for chronic cxs

Cholecystectomy for symptomatic gallstones

Splenectomy if indicated

455
Q

What are the indications for splenectomy in HA?

A

PK deficiency and some other enzymopathies

HS

Severe elliptocytosis and pyropoikilocytosis, thalassaemia, immune HA

Also if transfusion dependant, grwoth delay, physical limitaiton, Hb <8, hypersplenism

Don’t do under 3y/o but do before 10y/o to maximise prepubertal growth.

Risk of overwhelming sepsis

456
Q

Features of SCD

A

AR

Single base mutaiton; GAG-GTG. Glu-> Val at codon 6 on beta chain.

Leads to HbS instead of HbA

457
Q

What is the pathophysiology of HbS?

A

GAG->GTG

Glu-Val at codon 6 of beta chain

458
Q

Which Hb chain does SCD affect?

A

beta

459
Q

What are the possible genotypes and their phenotypes in SCD

A

HbSS: severe

HbAS: sickle cell trait, usually asymptomatic.

Rarer forms:

HbSC: Sickle cell HbC disease.(HbC has defective beta chain)

HbS/beta: Sickle Beta thalassaemia.

460
Q

Why does sickle cell anaemia manifest at 3-6m?

A

Coincides with decreasing fetal Hb (HbF)

461
Q

What is the pathophysiological mechanism for sickling?

A

Reduced O2 tension leads to HbS polymerisation and subsequent sickling

462
Q

What are the important features of SCA?

A

Anaemia 60-80g/L

Splenomegaly

Foalte deficiency

Gallstones

Aplastic crises (parvovirus B19)

463
Q

What are the vaso-occlusive features of Sickle-cell disease?

SICKLED

A

Stroke

Infections (hyposplenism, CKD)

Crises

Kidney: papillary necrosis, nephrotic syndrome

Liver: gallstones

Eyes: retinopathy

Dactilitis: impaired growth

Mesenteric iscahemic

Priapism

464
Q

What are the clinical features of a sickle cell crisis?

A

Splenic sequestration

Chest and pain

465
Q

How does the age of onset of SCD affect px

A

Child: strokes, splenomegaly, splenic crises and dactylitis.

Teens: impaired growth, gallstones, psych, priapism

Adult: hyposplenism, CKD, retinopathy, pulmonary HTN

466
Q

Dx of SCD

A

Sickle cells and target cells on blood film

Sickle solubility test

Hb electrophoreisis

Guthrie to test to aid prompt pneuomococcal prophylaxis

467
Q

Treatment of sickle cell disease

A

Analgesia for painful crises

Folic ACid

Penicllin V

Pneumovax

HiB vaccine

Hydroxycarbamide

Carotid doppler monitoring in early childhood with prophlyactic exchange transfusion if turbulent carotid flow

468
Q

Mechanism of hydroxycarbamide in SCD

A

Promotes production of HbF

469
Q

What is the pathology of thalassaemias?

A

Unbalanced Hb synthesis-> unmatched globins precipitate-> haemolysis and ineffective erythropoeisis

470
Q

What are the features of beta thalassaemia?

A

Point mutations leading to reduced beta chain synthesis, excess alpha cahins

Raised HbA2 and HbF

471
Q

What are the signs of beta-thalassaemia?

A

Skull bossing, maxillary hypertrophy, hairs on end skull XR

472
Q
A

In severely affected patients, a widening of the diploic space (medulla) with a thinning of the tables (cortices) occurs, frequently with complete obliteration of the outer table. New bone forms in response to marrow proliferation beneath the periosteum. These bony spicules may be seen radiographically and result in a classic “hair-on-end” appearance. Because it lacks hematopoietic marrow, the occipital bone usually is not involved. (See the image below.)

473
Q

What are the different types of beta thalassaemia?

A

Minor

Intermedia

Major

474
Q

What are the features of beta thalassaemia minor

A

Heteroztgous

Asmptomatic carrier

Mild anaemia

475
Q

What are the features of beta thalassaemia intermedia?

A

Moderate anaemia

Splenomegaly

Bony deformity

Gallstones

476
Q

What are the features of beta thalassaemia major

A

Homoxygous

3-6m severe anaemia

FTT

Hepatosplenomegaly

Bony deformity

Severe anaemia

Heart failure

477
Q

Mx of beta thalassaemia

A

Blood transfusions

Desferrioxamine

Folic acid

478
Q

Features of alpha thalasasaemia

A

Deletions in alpha chain of Hb: reduced synthesis and excess beta chains

Therea re 4 alpha genes, severity depends on number of genes deleted

479
Q

A thalassaemia trait

A

1/2 alpha genes deleted

Asymptomatic/ mild anaemia

480
Q

HbH

A

3 alpha chains deleted

Moderate anaemia

Splenomegaly

481
Q

4 alpha chains deleted

A

Hydrops foetalis- incompatibble with life

482
Q

What are the two tpyes of autoimmune HAs?

A

Warm and Cold

483
Q

What is the most common AIHA?

A

Warm

484
Q

What are the features of WAIHA?

A

37 degress

IgG

Positive Coomb’s

Spherocytes on blood film

485
Q

What Ig is associated with WAIHA?

A

IgG

486
Q

What are the features of cold agglutinin disease?

A

<37

IgM

Positive Coomb’s

Associated with Raynaud’s

487
Q

What Ig in cold agglutinin disease?

A

IgM

488
Q

What are the causes of WAIHA

A

Mainly idiopathic

Lymphoma, CLL, SLE, methyldopa

489
Q

Mx of WAIHA?

A

Steroids

Splenectomy

Immunosuppression

490
Q

Mx of cold agglutinin disease?

A

Treat underlying condition

Avoid the cold

Chlorambucil

491
Q

What is PCH?

A

Paroxysmal cold haemoglobinuria

492
Q

What are the features of PCH?

A

Hb in the urine usually caused by a viral infection e.g. measles, syphillis, VZV

Donath-Landsteiner Abs-> stick to RBCs in cold, lead to complement mediated haemolysis on reqarming.

493
Q

Donath-Landsteiner Abs seen in?

A

Paroxysmal cold haemoglobinuria

494
Q

What are the features of PNH

A

Acquired loss of protective surface GPI markers on RBCs (platelets and neutrophil) leads to complement mediated lysis.

This results in a chronic intravascular haemolysis, especially at night.

495
Q

What are the symptoms of PNH

A

Morning haemoglobinuria

Thrombosis (+ Budd Chiari syndrome)

496
Q

Dx of PNH

A

Immunophenotype shows altered GPI or Ham’s test

497
Q

What is Ham’s test?

A

In vitro acid induced lysis

Seen in PNH

498
Q

What is the treatment of PNH?

A

Iron/folate supplements

Prophlyactic vaccines/antibodies

Monocloncal abs e.g. eculizumab that prevents complement from binding RBCs

499
Q

What is the pathology of MAHA

A

Mechanical RBC destruction: forcedthrough fibrin/plt mesh in damaged vessels leading to schisotcytes

500
Q

Schistocytes=

Seen in?

A

RBC fragments

MAHA

501
Q

What are the causes of MAHA

A

HUS

TTP

DIC

Pre-ecl

502
Q

Rx in MAHA

A

PLEX

503
Q

What is the pentad of TTP?

A

MAHA

Renal impairment

Fever

Neurological abnromalities

Thrombocytopenia

504
Q

What are the features of HUS

A

Caused by E coli

Toxin damages endothelial cells-> MAHA

Diarrhoea

Renal failure

No neuro problems

Affects children and elderly

505
Q

What is the commonest leukaemia in te western world?

A

B Cell CLL

506
Q

Def: B Cell CLL

A

Proliferation of mature non-functioning B lymphocytes

507
Q

Epidoemiology of CLL

A

Caucasian and black population 20-30x more than Inidian, China, Japan

65-70y/o

40% of all leukaemias in people over 65

1/3rd >?75, 1/3rd< 65 1/3rd in between

508
Q

Natural history of CLL

A

Progressive accumulation of mature malignant B lymphocyts

Takes decades and may be a coincidental laboratory finding although can also present acutely

509
Q

What are the clinical issues with CLL

A

Proliferation in BM-> failure

Circulation in the nodes and spleen-> lymphadenopathy

Acquisition of further mutations can lead to a transformation to a high grade lymphoma

Can lead to autoimmune problems e.g. HA

510
Q

Where is CLL primarily seen?

A

BM

511
Q

Where is Small lymphocytic lymphoma seen?

A

LNs

512
Q

Clinical presentation of CLL

A

Incidental finding in routine bloods (80%)

Symmetrical painless lymphadenopathy

Splenomegaly

BM failure: anaemia & thrombocytopenia, recurrent infections

B symptoms: fevers, night sweats, weight loss

Associated with autoimmunity: AIHA, ITP

Can progress to a form of lymphoma (DLBC)- Richter’s transformation

513
Q

What is Richter’s transformation?

A

Richter’s syndrome (RS), also known as Richter’s transformation, is atransformation which occurs in about 5-10% of B cell chronic lymphocytic leukemia (CLL) and hairy cell leukemia into a fast-growing diffuse large B cell lymphoma, a variety of non-Hodgkin lymphoma which is refractory to treatment and carries a bad Px

514
Q

Ix in CLL

A

WCC: persistent lymphocytosis >5: morphology, immunophenotyping, cytogenetics. Composed of small mature lymphocytes

Low serum Ig

Smear cells seen on blood film

Abnormal BM: lymphocytic replacement of normal marrow

May also find immuneparesis and paraptroteins

515
Q

Smear cell

A

CLL

516
Q
A

CLL

Smear cell are cells that are damaged due to peripheral blood smear

Due to reduced strength of abnormal white cells in CLL

517
Q

Dx of CLL

A

Dx: small mature lymphocytes with smear cells

Immunophenotyping

Dx: lymphocytosis >5, smear cells, immunophenotyping: CD5 positive, CLL score

518
Q

DDx of CLL

A

CLL/SLL

Mantle cell lymphoma

519
Q

Good prognositc factors in CLL

A

Hypermutated IgG

Low Zap-70 expression

13q14 deletion

520
Q

Bad prognostic factors in CLL

A

Raised LDH

CD38+ve

11q23 del

521
Q

Px of CLL

A

50% of patients die of an unreleated cause

Incurable by CTx

No benefit to early treatment

522
Q

How can CLL be staged?

A

Binet and Rai Staging

523
Q

How is CLL stgaed using Binet

A

A

B

C

524
Q

Binet A

A

<3 lymphoid areas

525
Q

Binet B

A

>3 lymphoid areas

526
Q

Binet C

A

Hb <10

Plt <100

527
Q

How is CLL staged using Rai staging

A

0 - IV

528
Q

Rai Stage 0

A

Lymphocytosis only

Low risk

529
Q

Rai Stage I

A

Lymphadenopathy

530
Q

Rai Stage II

A

Intermediate risk

Hepatosplenomegaly +/- lymphadenopathy

531
Q

Rai Stage III

A

High Risk

Hb <11

532
Q

Rai Stage IV

A

plt <100

533
Q

ZAP70/CD38

A

Detected in CLL by immunophenotyping

Expression correlates with Ig status. Bad prognostic feature

534
Q

What is the worst prognositc facture in cytogenetics for CLL?

A

-17p (p53)

535
Q

Rx in CLL

A

Supportive treatment

Treatment of complications: immune haemolysis, disease transformation

CTx:

Stage A: conventional not to treat. Indications for treatment include BM failure, major or progressive lymphadenoapthy, progressive lymphocytosis, systemic symptoms, autoimmune cytopenias

536
Q

CTx in CLL

A

First line: FCR (fludarbine, cyclophosphamide, rituxmiab)

Oral chlorambucil for slow goa nd no go

17p needs different therapy

2nd line for <60y: consider allograft

537
Q

What is used for p53 mutated CLL

A

Campath/alemtuzumab

538
Q

Auotimmune complications of CLL

A

AIHA

Autoimmune thrombocytopenia

Neutropenia

Pure red cell aplsia

Mx with steroids

539
Q

PRCA

A

Pure red cell aplasia (PRCA) orerythroblastopenia refers to a type ofanemia affecting the precursors to red blood cells but not to white blood cells. In PRCA, the bone marrow ceases to produce red blood cells.

540
Q

Mx of high grade transformation in CLL

A

LN biopsy

CHOP-R

541
Q

Mx of infection risk in CLL

A

Prophylaxis and treatment of infection

Antibiotics

PCP rpophylaxis for those eceiving FDA or campath

IvIG for those with hypogammaglobulinaemia

Pneumovax and HiB

542
Q

Def: myelodysplastic syndromes

A

Biologically heterogeneous group of acquired HSCT disorders

Characterised by:

the development of aclone of marrow stem cells with abnromal maturation resulting in:

functionally defective blood cells and numerical reduction

Cytopenias

Functional abnromaltieies of erythroid, myeloid and megakaryocyte maturation

Increased risk of transformation to AML

Typically a disorder of the elderly

543
Q

Blasts in myelodysplastic syndromes?

A

<20

If it were greater than >20 it would be a leukaemia

544
Q

Clinical features of MDS?

A

Bm failure and cytopenias: infection, bleeding, fatigue

Hypercellular BM

Defective cells:

RBC: ring sederoblasts

WBC: hyogranulationn, pseudo Pelget Huet anomaly

PLatelets: micromegakaryotcytes, hyoablated nuclei

545
Q

What is Pelger-Huet anomaly

A

Neutrophil with bilobed Pelgroid nuclei.

Look identical to those seen in the inherited Pelger-Huet anomaly.

Neutrophil has markedly reduced granulation.

546
Q
A

Pelger-Huet Anomaly

Abnormality in neutrophils seen in MDS

547
Q

What are the abnormal bone marrow morphologies seen in MDS

A

Pelger Huet abnromaltiy

Dysgranulopoeisis of neutrophils

Myelokathexis of neutrophils and precursors (retention in BM)

Dyserythropoeisis

Dysplastic megakaryocytes

Increased proportion of blast cells

Ringed sideroblasts

548
Q

What are ringed sideroblasts?

A

Seen in refractory anaemia

Prussian blue stain of bone marrow shows blue staind haemosiderin deposits in the mitochondria of erythroid precurors forming an apparent ring around the nucleus

549
Q
A

Ringed sideroblasts

Seen in refractory anaemia

Prussian blue stain of bone marrow shows blue staind haemosiderin deposits in the mitochondria of erythroid precurors forming an apparent ring around the nucleus

550
Q
A

Auer rod

AML

551
Q
A

Myelokathexis

Bone marrow smear from a patient with neutropenia due to myelokathexis

552
Q

How can MDS be classified?

A

Marrow: dysplasia (? hypercellular)

RAEB-I

RAEB-II

Blood: cytopenias/defective cells

RA +/- RS (RARS)

RCMD

RCMD-RS

MDS 5q-

MDS unclassified

553
Q

Presentation of RA

A

Presents with anaemia

Can be with (RARS) or without ringed sideroblasts

554
Q

What is RCMD?

A

Refractory cytopenia with multilineage dysplasia

Presents with bicytopenia or pancytopenia

555
Q

What is RAEB-I

A

Refractory anaemia with excess blasts

BM blasts 5-10%

556
Q

RAEB-II

A

BM blasts 11-20%

557
Q

What is the presentation of MDS 5q-

A

Anaemia with normal platelets

558
Q

What is unclassified MDS

A

Presents with neutropenia or thrombocytopenia

MDS with fibrosis, childhood MDS etc.

559
Q

What is RAEB-T

A

Refractory anaemia with excess blasts in transofmration

Characterised by 21-30% myeloblasts in the marrow

Now considered AML

560
Q

How can MDS Px be scored?

A

International prognostic scoring system in MDS

BM blast %

Karyotype

Cytopenia

High risk >2.5

561
Q

What occurs in myelodysplasia evolution?

A

Deterioriation of blood counts- indicative of worseing consequence of marrow failure

Development of AML (50% in <1y). AML from MDS has a much poorer prognosis and is not curable

1/3rd die from infection, 1/3rd from bleeding, 1/3rd from leukaemia

562
Q

Treatment of MDS

A

Supportive: blood products, EPO, G-CSF, Abx

Biological modifiers: immunoscupressive therapy: lenalidomide, cytosine analgoue

CTx: similar to AML

Can also use hydroxyurea

Allogenic SCT

563
Q

What is azacytidine?

A

Cytosine analogue

564
Q

What is lenalidomide?

A

Thalidomide derivative. Anti-angiogenic, anti-tumour via apoptosis and anti-osetoclastogenic.

Used in MDS

565
Q

What causes bone marrow failure

A

Damage or suppression of stem (all peripheral bloood lines affected)

or progenitor cells (bi or unicytopenias

566
Q

How can BM failure be classified

A

Priamry

Secondary

567
Q

What are some primary causes of BM failure?

A

Congenital: Faconi’s anaemia

Diamond-Blackfan anaemia

Kostmann’s syndrome

Acquired: idiopathic aplastic anaemia (mutlipotent stem cell)

568
Q

What are the secondary causes of bone marrow failure?

A

Marrow infiltration

Haematological: leukaemias etc.

Non-haematological: solid tumours

RTx

Chemicals: benzenes

569
Q

What drugs can cause bone marrow fialure?

A

Predicatble: cytotoxic in dose-dependant fashion

Idiosyncratic: phyenlybutazone, gold salts (not dose dependant)

Abx: chloramphenicol, sulphonamide

Carbimazole, thiazides

570
Q

Def: aplastic anaemia

A

Inability of BM to produce red blood cells

HSC numbesr are reduced in BM

AA typically refers to just anaemia however these patients can also have a pancytopenia.

Symptoms relate to each cytopaenia

Patients typicallly present with bleeding problems

Can present at any age

571
Q

With what conditions is aplastic anaemia linked?

A

Leukaemia, PNH

572
Q

How can AA be classified?

A

Primary

Secondary

573
Q

What are the primary causes of AA

A

Idiopathic (70%): humoral or T cell attack against multipotent HSC

Inherited: dyskeratosis congenita, FA, Schwaman diamond syndrome

574
Q

What are the secondary causes of AA?

A

Due to malignant infiltration

Radiation

Durgs

Viruses

CTx

SLE

575
Q

Def: severe aplastic anaemia

A

2/3 of the following peripheral blood features:

<1% reticulocytes (<20x10^9)

Neutrophils (<0.5)

Plt (<20)

BM <20% cellularity

576
Q

DDx for pancytopenia and hypocellular marrow

A

Hypoplastic MDS/AML

Hypocellular ALL

Hairy cell leukaemia

Mycobacterial infection (atypical)

Anorexia

ITP

577
Q

What is NSAA?

A

Non-severe aplastic anaemia

578
Q

What is the clinical presentaiton of aplastic anaemia?

A

Classical triad:

Anaemia: breathlessness fatigue

Leukopenia: infections

Plt: easy brusing/bleeding

579
Q

Mx of aplastic anaemia

A

Supportive: blood products, antibitoics, Fe chelation

Marrow recovery drugs: oxymetholone, grwoth factors

Immunosuppressive therapy

SCT: young patietns iw th adonor

580
Q

Cxs of immunosuppressive therapy in AA?

A

Relapse of AA
Clonal haematological disorders: MDS and leukaemia.

PNH

581
Q

What are the inherited BM failure syndromes causing pancytopenias?

A

Fanconi Anaemia

Dyskeratosis congenita

Schwachman-Diamond syndrome

Familial aplastic anaemia (autosomal and X linked forms)

Myelodysplasia

Non-haematological syndormes e.g. DS, Dubowitz’s

582
Q

What are the inherited BM failure syndromes causing single cytopenias?

A

Diamond-Blackfan syndrome

Kostmann’s syndrome

Schwchman diamond syndrome

Reticular dysgenesis

Amegakaryocytic thrombocytopenia with abenst radii

583
Q

What is the inheritance of Fanconi anaemia

A

AR

584
Q

What are the features of Fanconi anaemia

A

Presents at 5-10yrs

Pancytopenia

Skeletal abnormalities: radii, thumbs, renal malformations, microopthalmia, short stature, skin pigmentation

MDS (30%), AML risk (10% progress)

585
Q
A

Fanconi anaemia

586
Q

Cxs of fanconi anaemia

A

Aplastic anaemia

Leukaemia

Liver disease

Myelodisplasia

Cancer (epithelial)

587
Q

What are the features of dyskeratosis congenita

A

X-linked

Chromosome instability (telomere shortening)

Skin pigmentation

Nail dystrophy

Oral leukoplakia

BM failure

588
Q

Nail dystrophy

Skin pigmentation

Oral leukoplakia

A

Triad seen in Dyskeratosis congenita

589
Q
A

Dyskeratosis congenita

590
Q

Features of Schwachman-Diamond syndrome

A

AR

Primarily neutropenia

Skeletal abnormalities, endocrine and pancreatic dysfunction, hepatic impairment, short stature

AML risk

591
Q

Features of Diamond-Blackfan syndrome

A

Pure red cell aplasia: normal WCC and plateltes

Presents at 1y

Dysmorphology

592
Q

Def: myeloproliferative disorders

A

A group of conditions characterised by clonal proliferation of one or more haematopoeitic component i.e. increased production of mature cells

Can be Ph+ve i.e. CML

or Ph-ve

593
Q

What are Ph-ve myeloproliferative conditiosn associated with?

A

JAK2 mutations

especially PCV

594
Q

What are the types of myeloproliferative disorders

A

PCV

Essential thrombocythaemia

Idiopathic myelofibrosis

Idiopathic erythrocytosis

CML

595
Q

What is the difference between myeloproliferative, myelodysplasia and leukaemia

A

MPD: proliferation and full differentiation

MDS: ineffective proliferation and differentiation

Leukaemia: proliferation without differentiation

596
Q

Polycythaemia

A

Riaed red cell mass

Hb

Red Cell count

PCV

597
Q

Causes of polycythaemia

A

Primary:

PCV

Familial polycythaemia

Secondary:

Raised EPO

(disease sates, renal Ca, high altitude, chronic hypoxia)

598
Q

What is pseudo polycthaemia?

A

Red cell mass normal but reduced plasma volume e.g. dehydration, burns, vomiting, diarrhoea, cigarette smoking

599
Q

Features of PCV

A

Predominant presentation of increasd RBCs

Production independent of normal erthropoeisis

Often a true increase in plasma volume

Increases with age

Point mutations of JAK2 (V617F)

600
Q

Point mutations of JAK2 (V617F)

A

PCV

601
Q

Cxs of PCV

A

Thrombosis occurs if platelets not reduced

Leukaemia may occur

Myelofibrosis may occur

602
Q

Clinical features of PCV

A

Incidental Dx on routine testing

Hyperviscosity/hypervolaemia/hypermetabolism: blurred vision, headaches, light-headedness, stroke, fatigue, dyspnoea

Plethroic: red nose, gout, thrombosis, retinal vein enorgement, erythromelagia

Splenomegaly

Increaseed histamein release: aquagenic pruritus (contact with water0 and peptic ulcers

603
Q

Ix in PCV

A

Raised Hb

Hct

May be increased platelets

WCC can be normal or increased

No blast cells

Increased red cell mass and plasma volume

BM: increased ceullarity mainly affecting erythroid cells.

Low serum EPO

JAK2 V617F mutation is dxic.

604
Q

How can blood volume be measured?

A

Isotope dilution method

605
Q

Diagnostic criteria for PCV

A

Raised RC mass >25%

Hb >18.5g/l in men, 16.5 in women

Absence of other causes of erythrocytosis

BM cellularity

606
Q

Treatment of PCV

A

Veensection

Hydroxycarbamide: cytoreductive therapy

Aspirin: keep platelets below 400

607
Q

Features of idiopathic erythrocytosis

A

Absence of JAK2 V617F mutation

Isolated erythrocytosis, low EPO

Less likely to turn to myelofibrosis or AML.

Treat with venesection only

608
Q

Features of esssential thrombocythaemia

A

Chronic MPD involving megakaryocytic lineage

Sustained plt >600

Incidence is at 55 and 30y

F>M at 55, equal at 30

609
Q

Clinical presentation of essential thrombocythaemia

A

Incidental

Thrombosis: arterial or venous, CBA, gangrene etc.

Bleeding: mucous membranes and cutaenous

Headaches, dizziness and visual disturbances

Modest splenomegaly

610
Q

Dx of essential thrombocythamia

A

Plt >600

Megakaryocyte abnormalities or clustering on blood film

No evidence of reactive thrombocytosis

No preceding or coincidental myeloproliferative disorder or dysplasia

Megakaryocytes in BM

611
Q

Mx of essential thrombocythaemia

A

Aspirin: thrombosis prevention

Anagrelide: reduces fromation of plts from megakaryocytes

Hydroxycarbamide: supress other cells

Alpha IFN in patients <40

612
Q

Px of essential thrombocythaemia

A

Normal lifespan may not be changed

Leuakaemic transofrmation in 5%

Myelofibrosis also uncommon

613
Q

Def: myelofibrosis

A

A clonal myeloproliferative disease with proliferation mainly of megakaryocytes and granulocytic cells associated with reactive bone marrow fibrosis and extramedullary haematopoiesis

614
Q

How can myelofibrosis be classified?

A

Primary: idiopathic

Secondary: following PRV, ET, leukaemia etc.

615
Q

Clinical presentation of idiopathic myelofibrosis

A

Elderly

Pancytopenia related symptoms

Extramedullary haematopoeisis- hepatomegaly, massive splenomegaly, WL, fever

Can present with budd-chiari syndrome

Hypermetabolic state: weigtht loss, fatigue, dyspnoea, night sweats, hyperuricaemia.

616
Q

BM dry tap

A

Myelofirbrosis

617
Q

Tear drop poikilocytes, (dacrocyte) leukoerythroblasts

A

Myelofibrolsis

618
Q

What are the stages of myelofirgbosis?

A

Prefibrotic stages: mild blood changes, hypercellular marrow.

Fibrotic stage:

Liver and spleen: splenogmealy and extramedullary haemopoiesis

Blood changes: leucoerythroblastic picture, tear drop poikilocytes, giant platelets, circulating megakaryocytes

BM: dry tap, prominent collagen fibrosis and reticulin. New bone formation and osteosclerosis later

619
Q

Treatment of myelofibrosis

A

Anaemia: transfusion (become difficult because of splenomegaly- splenectomy)

Plt

Cytoreductive therapy: hydroxycarbamide

Thaildomide with or without prednisolone

BM transplant (experimental)

620
Q

What are the bad prognostic signs in myelofibrosis?

A

Severe anaemia

Thrombocytopenia

Massive splenomegaly

621
Q

What is the relationship between EPO/TPO and JAK2

A

Normally stimulate the receptor that is associated with JAK2.

622
Q

Prevalence of JAK2 mutations in myeloproliferative disorders

A

PCV 99%

ET 50%

IM 50%

623
Q

What is the MTD for bone marrow?

A

Maximum tolerated dose of radiation 1gy12gy

624
Q

When are there cerebrovascular events following radiation?

A

>30gy

625
Q

What are the methods for SCT?

A

Autologous

Allogenic

626
Q

Features of autologous BM transplant

A

Give patient growth factors, collect SC and freeze them.

Thaw and reinfuse after high dose CTx

Indicated in acute leukaemia, lymhpoma, solid tumours, myeloma, CLL

627
Q

Features of allogenic SCT

A

Patient is given high dose RTx and CTx and bone marrow or peripheral blood stem cells are transfused from a matched donor

Indicated in acute leukaemia, chronic leukaemia, myeloma, BM failure, congenital immune deficiencies, lymphoma

628
Q

What are the complications of SCT?

A

Graft failure

Infections

GvHD

Relapse

629
Q

Mx of GvHD

A

Corticosteroids

Cyclosporine

Tacroliums

Mycophenylate mofetil

Monoclonal Abs

Photophersis

Total lymphoid irradiation

630
Q

What are the different phases following allogenic BMT

A

Aplastic phase (0-3w): Gram positive and negative bacteria, candida, sV, RSV

GvHD phase (3w-3/6m): CMV, VZV, HHV, aspergillus, candida, adenovirus

Late phase (6m-yeasr): pneuomoccoal, H influenza, VZV

CMV is the prime suspect in transplant patients.

631
Q

When can the first mutation for ALL occur?

What can happen

A

Can occur in utero

Pre-leukaemic cells carrying this mutation can spread from one twin to another

632
Q

What is TAM

A

Transient abnromal myelopoiesis is a specific type of neonatal leukaemia.

Myeloid leukaemia with major involvement of the megakaryocyic lineage

Remits spontaneously but relapse can occur 1-2 years later in 1/4

633
Q

WCC

Neutrophil

Lymphocyte

Hb

MCV

In neonate

A

26.1

15

10

220

120

634
Q

WCC

Neutrophil

Lymphocyte

Hb

MCV

In 2 year old

A

10.1

2

7

110

75

635
Q

WCC

Neutrophil

Lymphocyte

Hb

MCV

In adult

A

4-11

2-7.5

  1. 3-4
  2. 5-16.5 and 13-18

77-95

636
Q

Hb in children

A

No gender difference

637
Q

Why may vit deficiencies manifest in childhood?

A

Due to rapid growth

Fe deficiency common during growth spurt

FOlica acid deficiency can also occur

638
Q

What can cause polycythaemia in nneonates?

A

TTTS

Intrauterine hypoxia

Placental insufficiency

639
Q

What can cause anaemia in neonate?

A

TTTS

Foetal to maternal transfusion

Parvovirus infection

Haemorrhage from the cord of placenta

640
Q

Structure of HbA

A

a2b2: present in late foetus, infant, child and adult

641
Q

HbA2

A

A2D2, present in the infant, child and adult

642
Q

HbF

A

A2G2, present in foetus and infant

643
Q

Normal Hb beta chain gene cluster

Sickle cell trait

Sickle cell disease

Sickle cell c

Sickle cell/beta thal

A

beta beta

beta betas

betas betas

betas betac

betas betathal

644
Q

Why does Sickle cell disease differ between children and adult?

A

Different distribution of red bone marrow: susceptible to infarction

dactylitis, acute chest syndrome, painful crisis, stroke

Infant has funcitoning spleen

splenic sequestration: severe anaemia, schock and death.

Imamture immune system means they are more susceptible to pneumococcus and parvovirus

First exposure to parvovrius will lead to RCA

Infant has higher requirements for folic acid

hyperplastic erythropoeisis requires folic acid

645
Q

What is splenic sequestration

A

Acute pooling of a large percentage of circulating red cells in the spleen

Leads to acute splenic enlargement and reduciton in Hb

646
Q

Clinical effects of poorly treated thalassaemia major

A

Anaemia: heart failure and growth retardation

Erythropoietic driveL bone expansion, hepatomegaly, splenomegaly.

Fe overload: heart and gonadal failure

647
Q

What are the types of inherited defects of coagulation?

A

Haemophilia A

B

Von Willebrand disease

648
Q

What factor is affected in haemophilia A?

A

Factor VIII

649
Q

What factor is affected in haemophilia B?

A

Factor IX

650
Q

Presentation of haemophilia

A

Bleeding after circumcision

Haemarthrosis when starting to walk

Bruises and post-traumatic bleeding

651
Q

Dx of haemophilia

A

Umbilical cord bleeding

Heel prick

Haematoma formation after injections

FHx

Coagulation screen

Plt count

Assay of specific coagulation factors

652
Q

Mx of haemophilia

A

Dx

Counselling

Treatment of bleeding epsidoes

Use of prophylactic coagulation factors

653
Q

Presentation of Von Willebrand

A

Mucosal bleeding, brusies and post-traumatic bleeding

654
Q

Presentaiton of autoimmune thrombocytopenic purpurae?

A

Petechiae, bruises, blood blisters in mouth

Ddx: henoch schonlein, NAI, coagulation factor defected

655
Q

Mx of AITP?

A

Observation

Corticosteroids

High dose IVIG

IV anti-RhD if Rh-positive

656
Q

When is AML more common than ALL in children

A

In those <1y/o

657
Q

Causes of gangrene

A

Vascular: peripheral vascular disease

Blood: PCV, cold agglutinin, essential thrombocythaemia

658
Q

What blood abnormalities are associated with RA?

A

Anaemia of chronic disease

Fe deficiency due to aspirin or NSAID use

Neutropenia or thrombocytopenia from NSAID use

Felty’s syndrome

Increased ESR

659
Q

Felty’s syndrome

A

RA

Splenomegaly

Neutropenia

660
Q

Child with swollen single joint

A

Haemophilia

NAI

Osteomyelitis

Septic arthritis

661
Q

Mx of TTP

A

PLEX

662
Q

Draw the process of haemostasis

A
663
Q

What are the constituents of the priamry platelet plug

A

Platelets

VW factor

Vascular endothelium

664
Q

What are the functions of the endothelium?

A

Synthesis PGI2

VwF

Plasminogen activators

Thrbomomdoulin

Acts as the main barrier between the blood and the procoagulant subendothelium

665
Q

What is VW factor?

A

Glycoprotein made in endothelium and platelts.

Monomers link to form a large multimeric protein

Each vWF monomer has a binding domain for platelets, collagen and factor VIII

666
Q

What is the lifespan of a platelt?

A

10d

1/3rd stored in the spleen

667
Q

Draw the coagulation cascade

A
668
Q

Draw the process of platelet adhesion and aggregation

A
669
Q

Draw the process of arachidonic acid metabolism

A
670
Q

What factors are involved in fibrinolysis

A

Anthithrombin binds to FXa to form antibthrombin complex

Activity/binding is increased by heparin

Protein C/ Protein S

Plasmin: plasminogen activated via tPA, this breaks down fibrin clot to produce fibrin degradation productions

671
Q

What acquired defects lead to haemorrhagic disorder?

A

Liver disease

Vit K deficiency

AI disease e.g. platelet destruction, trauma, DIC, scurvy

672
Q

What inherited factors lead to haemorrhagic disorders?

A

Platelet abnormalities

Blood vessel wall abnormalities

Clotting factor deficiencies

Excess fibrinolysis

673
Q

What differentiates between disorders of platelets and disorders of coagulation factors?

A

Site of bleeding: skin, mucuous membranes. Coagulation factor is in soft tissues, joints, mmuscles.

Petechiae seen in platelet disorders

Small superficial echymoses, large deep in coagulation

haemarthroses common in coagulation factor

Bleeding after cuts and scratches seen in platelet disorders

Often severe delayed bleeding after surgery in coagulation

674
Q

What causes the differnece in the characteristics of platelt and coagulation factor disorders

A

Platelets are involved in priamry haemostasis

Coagulation factors are involved in the formation of fibrin clot

675
Q

How can platelet disorders be classified?

A

Decreased number

Defective funciton

ITP

676
Q

What are somecauses of decreased platelet number?

A

Decreased produciton

Decreased survival

Increased utilisation

Abnormal distribution

677
Q

What are some causes of defective platelet function?

A

Aspirin

Thrombasthenia

678
Q

What are the feautres of Glanzmann’s thrombasthenia

A

Rare congenital coagulopathy where platelets lack GIPIIb/IIIa

This means that fibrin crosslinking can occur

679
Q

Acquired causes of coagulation factor disorders?

A

DIC, liver diease, Vit K deficiency, warfarin overdose

680
Q

APTT in haemophilia

A

Prolonged

681
Q

Lab features of DIC

A

Prolonged APTT

PT

TT

682
Q

Mx of clotting disorders in liver disease

A

For prolonged PT/PTT: Vit K

For low fibrinogen: cryoprecipitate, fibrinogen concentrate

For DIC: (elevated d-dimer), replacement therapy

683
Q

Acanthocytse (spur/spike cells)

A

RBCs showing many spicules

Seen in abetalipoproteinaemia, liver disease, hyposplenism

684
Q

Basophilic RBC stippling

A

Accelerated erythropoeisis or defective Hb synthesis. Small dots seen at the periphery (rRNA)

Lead poisoning, megaloblastic anemia, myelodysplasia, liver disease, Hbopathy e.g. thalassaemia

685
Q

Burr cells (ecinthocyte)

A

Irregulalry shaped cells

Uricaemia, GI bleeding, stomach carcinoma

686
Q

Heinz Bodies

A

Inclusions within RBCs of denatured Hb

G6PD

Chronic liver disease

687
Q

Howell-Jolly bodies

A

Basophilic nuclear remnants in RBCs

Post-splenectomy or hyposplenism (e.g. SCD, coeliac, congenital, UC/Crohns, myeloproliferative disease, amyloid)

Megaloblastic anaemia

Hereditary spherocytosis

688
Q

Leucoerythroblastic anaemia

A

Marrow infiltration: nucleated RBCs and primitive WBCs in peripheral blood

Marrow infiltration i.e. myelofibrosis, malignancy

689
Q

Polychromasia

A

Sign of reticulocytes.

Red blood cells of multiple colours due to differing amounts of Hb in RBC

Premature/inappropriate release from BM

690
Q

Reticulocytes

A

Immature RBCs show mesh like network of ribosomal RNA which becomes visislbe with certain stains i.e. methylene blue.

Increased in HA

decreased in AA

691
Q

Right shift

A

Hypermature white cells (hypersegmented polymorphs >5 lobes to nucleus)

Megaolblastic anaemia, uraemia, liver disease

692
Q

Rouleaux formation

A

Red cells stacked on one another

Chronic inflammation

Paraproteinemia

MM

693
Q

Stoamtocytes

A

Central pallor is straight or curved rod-like shape. RBCs appear as smiling faces or fish mouth

Hereditary stomatocytosis, high ETOH, liver disease

694
Q

Target cells (codocyte)

A

Bull’s eye appearance in central pallor

Liver disease, hyposplenism, thalassaemia, IDA

695
Q

Def: anaemia

A

Men <13.5 Women <11.5

696
Q

Causes of anaemia

A

Reduced production

Increased loss

Increased plasma volume

697
Q

Symptoms and signs of anaemia

A

Fatigue, dyspnoea, faintness, palpitations, headache, tinnitus, anorexia

Pallor

Hyperdynamic circulation e.g. tachycardia, flow murmurs leading to hert failure (severe anaemia- <8)

698
Q

Causes of microcytic anaemia

FAST

A

Fe deficiency

Anaemia of chronic disease

Sideroblastic anemia

Thalassaemia (in the absence of anaemia)

699
Q

Causes of normocytic anaemia

A

Acute blood loss

Anaemia of chronic disease

BM failure

Renal failure

Hypothyroidsim

Haemolysis

Pregnancy

700
Q

Causes of macrocytic anaemia

FATRBC

A

Fetus (pregnancy)

Antifolates (phenytoin)

Thyroid (hypo)

Reticulocytosis

B12 or folate deficiency

Cirrhosis (ETOH excess of liver disease)

Myelodysplastic syndromes

701
Q

Signs of IDA

A

Koilonychia

Atrophic glossitis

Angular cheilosis

Post cricoid webs (Plummer vinson syndrome)

Brittle hair and nails

702
Q

Blood film in IDA

A

Microcytic

Hypochormic

Anisocytosis (varying size)

Poikilocytosis (varying shape)

Pencil cells

703
Q

IDA=

A

Blood loss until proven otherwise

704
Q

Causes of IDA

A

Blood loss

Increased utilisation

Decreased intake

Decreased absoprtion

Intravascular haemolysis

705
Q

Blood loss in IDA

A

GI loss

Meckel’s diverticulum

Peptic ulcers, gastritis

Polyps/CRC (most common cause in adults >50)

Menorrhagia

Hookworm infestation

706
Q

Increased utilisation IDA

A

Pregnancy

Lactation

Growth in children

707
Q

Decreased intake IDA

A

Prematurity

Infants/children/elderly

Loss of Fe each day fetus is not in utero.

Suboptimal diet

708
Q

Decreased absorption IDA

A

Coeliac

Post-gastric Sx

Absence in villous surphace of duodenum

Rapid transit: reduced acid which normally helps Fe absoprtion

709
Q

Intravascular haemolysis IDA

A

MAHA

PHA

Chornic loss of Hb in urine

710
Q

Treatment of IDA

A

Treat cause

Oral Fe

711
Q

Side effects of oral Fe

A

Nausea

Abdo discomfort

Diarrhoea

Constipation

Black stools

712
Q

Pathophysiology of anaemia of chornic disease

A

Inflammatory cytokines (IFNs, TNF, IL1) reduce EPOR production and thus EPO synthesis in kidneys

Fe metabolism is dysregulated: IL6 and LPS stimulate liver to make hepcidin which decreases Fe absortion from the gut through transferrin inhbition and causes Fe accumulation in macrophages

713
Q

Causes of ACD

A

Chronic infection

Vasculitis

RA

Malignancy

714
Q

Anaemia of chronic disease in renal failure

A

Not cytokine deficiency but due to EPO deficiency

715
Q

Ferritin in ACD

A

High due to sequestered Fe in macrophages unless the patient has coexisting IDA

716
Q

Sideroblastic anaemia causes

A

Ineffective erythropoeisis: Fe loading causes haemosiderosis

717
Q

Causes of sideroblastic anaemia?

A

Myelodysplastic disorders

Following CTx

Irradiation

ETOH excess

Pb excess

Anti-TB drugs

Myeloproliferative disease

718
Q

Rx of sideroblastic anaemia

A

Remove cause

Vitamine B6

719
Q

NB with ferritin

A

Acute phase marker

Check CRP with every raised ferritin seen in clinical practice

720
Q

Causes of macrocytosis

A

Megaloblastic

Non-megaloblastic

Other haematological disease

721
Q

Causes of megaloblastic macrocytosis

A

B12 deficiency

Folate deficiency

Cytotoxic drugs

722
Q

Causes of non-megaloblastic macrocytosis

A

ETOH (most common cause of macrocytosis without anaemia)

Reticulocytosis

Liver disease

Hypothyroidsim

Pregnancy

723
Q

Other haematological disease leading to macrocytosis

A

Myelodysplasia

Myeloma

Myeloproliferative disorders

Aplastic anaemia

724
Q

Megaloblastic blood film=

A

Hypersegmented polymorphs

Leucopenia

Macrocytosis

Anaemia

Thrombcoytopenia

725
Q

Sources of Vit B1

A

Meat and dairy products (large body stores)

726
Q

Causes of B12 deficiency?

A

Dietary

Malabsorption (stomach- pernicious anaemia, terminal ileum- resection in Crohn’s, bacterial overgrowth, tropical sprue, tapeworms

727
Q

Clinical features of B12 deficiency?

A

Mouth: glossitis, angular cheilosis

Neuropsychiatric: irritability, depression, psychosis, dementia

Neurological: paraesthesia, peripheral neuropathy (loss of vibration anjd proprioception first, absent ankle reflex, spastic parpereisis, SACD of SC)

728
Q

Tests for Pernicious anaemia

A

Parietal cell Abs

IF Abs

729
Q

Treatment of B12 deficiency

A

IM hydroxycobalamin

730
Q

Dietary sources of folate

A

Green vegetables

Nuts

Yeast

Liver

Low body stores cannot produce de novo

731
Q

Causes of folate deficiency

A

Poor diet

Increased demand

Malabsorption

Drugs: ETOH, anti-epileptics, methotrexate, trimethoprim

732
Q

Treatment of folic acid deficiency

A

Give oral folic acid

If cause of anaemia is not known then folic acid must not be given as it will exacerbate the neuropathy of B12 deficiency

733
Q

What to remember in coagulation pathway INTRINSIC

A

Next factor starts iwth letter of previous factor

734
Q

What test examines the intrinsic pathway

What can it monitor?

A

APTT

Heparin therapy

735
Q

What test monitors the extrinsic pathway?

What can it be used to monitor?

A

PT

Warfarin therapy

736
Q

What test can be used to examine the common pathway?

A

TT

737
Q

What are some congenital and acquired vascular defects

A

Congenital: Osler-Weber-Rendu syndrome, Ehlyer’s danlos

Senile purpura

Infection

Steroids

Scurvy

738
Q

Osler Weber Rendu

A

Osler-Weber-Rendu disease (OWRD) is a rare autosomal dominant disorder that affects blood vessels throughout the body (causing vascular dysplasia) and results in a tendency for bleeding. (The condition is also known as hereditary hemorrhagic telangiectasia [HHT]; the two terms are used interchangeably in this article.) The prognosis varies, depending on the severity of symptoms; generally, it is good, as long as bleeding is promptly recognized and adequately controlled.

HHT is manifested by mucocutaneous telangiectases and arteriovenous malformations (AVMs), a potential source of serious morbidity and mortality.[1]Lesions can affect the nasopharynx, central nervous system (CNS), lung, liver, and spleen, as well as the urinary tract, gastrointestinal (GI) tract, conjunctiva, trunk, arms, and fingers.

739
Q

Mx of Chronic ITP

A

Seen in adults

Doesn’t resolve spontaenously

Requires IVIG, steroids, splenectomy

740
Q

Dx of Haemophilia A

A

Raised APTT, Normal PT, reduced factor VIII assay

741
Q

Mx of Haemophilia A

A

Avoid NSAIDs and IM injections

Desmopressin

Factor VIII concentrates which is life long

742
Q

What is Christmas Disease?

A

Haemophilia B

Factor 9 deficiency

743
Q

Dx of vWD

A

Increased APPT

Increaesd bleeding time

Reduced Factor VIII (vWF is a carrier)

Reduced vWF concentrates

744
Q

Buses that go down high street ken

27, 9 and 10

A

Clotting factors requiring vitamin K for synthesis

745
Q

INR

APTT

TT

Plt

Bleeding time

In heparin

A

Raised

Raised ++

Raised ++

N

N

746
Q

INR

APTT

TT

Plt

Bleeding time

in DIC

A

Raised ++

Raised ++

Raised ++

Redcued

Increased

with raised d-dimer

747
Q

INR

APTT

TT

Plt

Bleeding time

in liver disease

A

Raised

Raised

N/raised

N/decreased

N/ raised

Transaminases elevated

748
Q

INR

APTT

TT

Plt

Bleeding time

In platelet defect

A

N

N

N

N

Raised

749
Q

INR

APTT

TT

Plt

Bleeding time

in Vit K deficiency

A

Raised ++

Raised

N

N

N

750
Q

INR

APTT

TT

Plt

Bleeding time

In haemophilia

A

N

Raised ++

N

N

N

751
Q

INR

APTT

TT

Plt

Bleeding time

in vWF

A

N

Raised ++

N

N

Raised

752
Q

The main component involved in stabilising the primary haemostatic plug.

A.

Fibrinogen

B.

Megakaryocyte

C.

Fibrin

D.

Erythrocyte

E.

Tissue plasminogen-activator (t-PA)

F.

Protein C

G.

Antithrombin III

H.

Plasmin

I.

Thromboxane A2

J.

a2 macroglobulin

K.

Cycloxygenase

L.

Platelet

M.

Endothelial cell

A

Fibrin

753
Q

A serine protease which assists in the break down of blood clots by binding to the clot and localising agents which break it down.

A

TpA

754
Q

A potent inhibitor of plasmin in the blood.

A

a2 microglobulin

755
Q

A 25 year old man presents to the Emergency Department a day after attending his dentist for a routine check-up. After treatment at the dentists the previous day, his gums had not stopped bleeding. On investigation, his APTT and bleeding time are prolonged but a normal PT.

A.

Autoimmune thrombocytopenic purpura

B.

Factor VIII deficiency

C.

Christmas disease

D.

Megakaryocyte

E.

Factor XII deficiency

F.

Thromboxane A2

G.

von Willebrand deficiency

H.

Sensitised platelet

I.

Haemophilia

J.

Marfan syndrome

K.

Vitamin K deficiency

L.

Ehlers-Danlos syndrome

M.

Prostacyclin PGI2

A

vWD

756
Q

A 16 year old girl presents to the Haematology Outpatients clinic describing a fluctuating history of easy bruising, epistaxis and menorrhagia. On investigation there is a thrombocytopaenia with increased megakaryocytes on BM examination

A.

Autoimmune thrombocytopenic purpura

B.

Factor VIII deficiency

C.

Christmas disease

D.

Megakaryocyte

E.

Factor XII deficiency

F.

Thromboxane A2

G.

von Willebrand deficiency

H.

Sensitised platelet

I.

Haemophilia

J.

Marfan syndrome

K.

Vitamin K deficiency

L.

Ehlers-Danlos syndrome

M.

Prostacyclin PGI2

Response Feedback:

F

A

AITP

757
Q

Which protein, important in haemostasis, is vitamin K dependent but is not a serine protease?

A

Protein S

758
Q

Which key clotting factor activates both factors V and VIII, and also activates protein C?

A

Thrombin

759
Q

Which option is required as a cofactor for protein C activity?

A

Protein S

760
Q

A 37 year old mother of 4 children, presents to her GP because of recurrent nose bleeds and feeling tired all the time and heavy periods.

A.

Sickle cell anaemia

B.

Factor V Leiden

C.

Christmas Disease

D.

Warfarin overdose

E.

Henoch – Schönlein Purpura

F.

Bile acid malabsorption

G.

Antiphospholipid antibody syndrome

H.

Malignancy

I.

Disseminated intravascular coagulation

J.

Vitamin K Deficiency

K.

Osler-Weber-Rendu Syndrome

L.

Haemophilia A

M.

Von Willebrand’s Disease

N.

B-Thalassaemia

A

Osler Wever Rendu

1) A rare autosomal dominant disorder. Alternative name = hereditary haemorrhagic telangiectasia. There is a structural abnormality of the blood vessels, resulting in telangiectases, which are thin walled so are likely to bleed. This leads to haemorrhage and anaemia. It is more common in females, and may not present until later in life. Epistaxis is the commonest presenting symptom. This patient is feeling tired, not just because of her 4 children, but because she also has iron deficiency anaemia.

761
Q

22 year old Saharawi refugee presents with anaemia, weight loss, loose stools and blood tests reveal an increased PT and slightly increased APTT, with normal thrombin time and platelet count.

A.

Sickle cell anaemia

B.

Factor V Leiden

C.

Christmas Disease

D.

Warfarin overdose

E.

Henoch – Schönlein Purpura

F.

Bile acid malabsorption

G.

Antiphospholipid antibody syndrome

H.

Malignancy

I.

Disseminated intravascular coagulation

J.

Vitamin K Deficiency

K.

Osler-Weber-Rendu Syndrome

L.

Haemophilia A

M.

Von Willebrand’s Disease

N.

B-Thalassaemia

A

Vit K deficiency

revalence of coeliac disease is highest in Saharawi refugees. This patient has coeliac disease, and as a result of malabsorption is losing weight and has loose stools (steatorrhoea), and vitamin K deficiency. The blood results related to vitamin K deficiency.

762
Q

A 5 year old boy has the following blood results: normal PT, increased APTT, normal platelet count, decreased VIII:C and decreased vWF.

A.

Sickle cell anaemia

B.

Factor V Leiden

C.

Christmas Disease

D.

Warfarin overdose

E.

Henoch – Schönlein Purpura

F.

Bile acid malabsorption

G.

Antiphospholipid antibody syndrome

H.

Malignancy

I.

Disseminated intravascular coagulation

J.

Vitamin K Deficiency

K.

Osler-Weber-Rendu Syndrome

L.

Haemophilia A

M.

Von Willebrand’s Disease

N.

B-Thalassaemia

A

The most common hereditary bleeding disorder, affect 1% of the population. vWF is a carrier protein for factor VIII and stabilises it. Mutation is in chromosome 12.

763
Q

Dangerous combination with no added efficacy and increased GI bleed.

A.

Dalteparin (LMWH)

B.

Aspirin

C.

10mg, 10mg, 5mg, measure on 4th day then every 2 days

D.

APTT

E.

Calciparone

F.

Pentapolysaccharide

G.

Clopidogrel

H.

Warfarin

I.

Prothrombin time (PT)

J.

Clopidogrel and aspirin

K.

5mg, 5mg, 5mg, 5mg, measure on 5th day, 8th day and then every 4 days

L.

Thrombin time (TT)

M.

LMWH and aspirin

N.

Dipyridamole modified release (MR) and aspirin

O.

Unfractionated heparin (UFH)

P.

Streptokinase

A

Clopidogrel and aspirin

764
Q

Old model of starting warfarin

A.

Dalteparin (LMWH)

B.

Aspirin

C.

10mg, 10mg, 5mg, measure on 4th day then every 2 days

D.

APTT

E.

Calciparone

F.

Pentapolysaccharide

G.

Clopidogrel

H.

Warfarin

I.

Prothrombin time (PT)

J.

Clopidogrel and aspirin

K.

5mg, 5mg, 5mg, 5mg, measure on 5th day, 8th day and then every 4 days

L.

Thrombin time (TT)

M.

LMWH and aspirin

N.

Dipyridamole modified release (MR) and aspirin

O.

Unfractionated heparin (UFH)

P.

Streptokinase

A

10mg, 10mg, 5mg, measure on 4th day then every 2 days

765
Q

Tait model of starting warfarin

A

5mg, 5mg, 5mg, 5mg, measure on 5th day, 8th day and then every 4 days

766
Q

Side effects include cutaneous necrosis

A.

Dalteparin (LMWH)

B.

Aspirin

C.

10mg, 10mg, 5mg, measure on 4th day then every 2 days

D.

APTT

E.

Calciparone

F.

Pentapolysaccharide

G.

Clopidogrel

H.

Warfarin

I.

Prothrombin time (PT)

J.

Clopidogrel and aspirin

K.

5mg, 5mg, 5mg, 5mg, measure on 5th day, 8th day and then every 4 days

L.

Thrombin time (TT)

M.

LMWH and aspirin

N.

Dipyridamole modified release (MR) and aspirin

O.

Unfractionated heparin (UFH)

P.

Streptokinase

A

Warfarin

767
Q

The drug most likely to cause thrombocytopaenia with paradoxical thrombosis

A.

Dalteparin (LMWH)

B.

Aspirin

C.

10mg, 10mg, 5mg, measure on 4th day then every 2 days

D.

APTT

E.

Calciparone

F.

Pentapolysaccharide

G.

Clopidogrel

H.

Warfarin

I.

Prothrombin time (PT)

J.

Clopidogrel and aspirin

K.

5mg, 5mg, 5mg, 5mg, measure on 5th day, 8th day and then every 4 days

L.

Thrombin time (TT)

M.

LMWH and aspirin

N.

Dipyridamole modified release (MR) and aspirin

O.

Unfractionated heparin (UFH)

P.

Streptokinase

A

UFH

768
Q

Indicated as thrombotic prophylaxis in DIC

A.

Dalteparin (LMWH)

B.

Aspirin

C.

10mg, 10mg, 5mg, measure on 4th day then every 2 days

D.

APTT

E.

Calciparone

F.

Pentapolysaccharide

G.

Clopidogrel

H.

Warfarin

I.

Prothrombin time (PT)

J.

Clopidogrel and aspirin

K.

5mg, 5mg, 5mg, 5mg, measure on 5th day, 8th day and then every 4 days

L.

Thrombin time (TT)

M.

LMWH and aspirin

N.

Dipyridamole modified release (MR) and aspirin

O.

Unfractionated heparin (UFH)

P.

Streptokinase

A

Dalteparin (LMWH)

769
Q

A 65 year old patient presents with hepatosplenomegaly. He is mildly anaemic and thrombocytompenic. A blood monocyte count of 1.2 x 109/l is observed. Bone marrow aspirate reveals ring sideroblasts at 15% of total blasts. Auer rods are observed.

A.

Refractory Anaemia with Ring Sideroblasts

B.

Acute Myeloid Leukaemia

C.

Chronic Myelomonocytic Anaemia

D.

Refractory Anaemia with excess of Blasts II

E.

Myelodysplastic syndrome,unclassifiable

F.

Refractory Cytopaenia with Multilineage Dysplasia

G.

Refractory anaemia

H.

Aplastic Anaemia

I.

Secondary Sideroblastic Anaemia

J.

Refractory Anaemia with excess of Blasts I

K.

Myelodysplastic syndrome associated with isolated del(5q) chromosome abnormality (5q syndrome)

A

CML

770
Q

A 58 year old lady complains of lethargy and “easy bruising”. She presents with purpura. Her FBC reveals Hb 10.5g/dl; WBCs 2.3x109/l and platelets 8x109/l. Blood film reveals <1% Blasts, and marrow aspirate shows 20% dysplasia in erythroid lineage, 60% dysplasia in platelet lineage, 5% dysplasia in granulocyte lineage, and less than 5% blasts.

A.

Refractory Anaemia with Ring Sideroblasts

B.

Acute Myeloid Leukaemia

C.

Chronic Myelomonocytic Anaemia

D.

Refractory Anaemia with excess of Blasts II

E.

Myelodysplastic syndrome,unclassifiable

F.

Refractory Cytopaenia with Multilineage Dysplasia

G.

Refractory anaemia

H.

Aplastic Anaemia

I.

Secondary Sideroblastic Anaemia

J.

Refractory Anaemia with excess of Blasts I

K.

Myelodysplastic syndrome associated with isolated del(5q) chromosome abnormality (5q syndrome)

A

Re Q3, to count as significant, dysplasia must involve at least 10% of cells in a lineage. To count as RCMD, at least 2 MYELOID lineages must be dysplastic, and there must be bi or pancytopenia in the peripheral blood. (This can include anaemia!)

771
Q

A 78 year old male patient with recurring infections of the face and maxillary sinuses associated with neutropenia. His bloods are: Hb 9.8 g/dl; WBC 1.3x109/l; Neutrophils 0.3x109/l; platelets 38x109/l.The lab informs you that there are Blasts approximately compromise 17% of bone marrow aspirate

A.

Refractory Anaemia with Ring Sideroblasts

B.

Acute Myeloid Leukaemia

C.

Chronic Myelomonocytic Anaemia

D.

Refractory Anaemia with excess of Blasts II

E.

Myelodysplastic syndrome,unclassifiable

F.

Refractory Cytopaenia with Multilineage Dysplasia

G.

Refractory anaemia

H.

Aplastic Anaemia

I.

Secondary Sideroblastic Anaemia

J.

Refractory Anaemia with excess of Blasts I

K.

Myelodysplastic syndrome associated with isolated del(5q) chromosome abnormality (5q syndrome)

A

Refractory Anaemia with excess of Blasts II

772
Q

A 74 year old woman with high-normal platelet count. Bone marrow aspirate shows hyperplasia of hypolobulated micromegakaryocytes. Responds well to lenalidomide.

A.

Secondary aplastic anaemia

B.

5q syndrome

C.

Idiopathic aplastic anaemia

D.

Acute myeloid leukaemia

E.

Inherited aplastic anaemia

F.

Myelofibrosis

G.

Refractory cytopenia with multilineage dysplasia

H.

Juvenile myelomonocytic leukaemia

I.

Refractory anaemia with an excess of blasts

J.

Refractory anaemia

A

5q syndrome

773
Q

In this case haemoglobin is normal but there is a reduction in platelets and neutrophils

A.

Secondary aplastic anaemia

B.

5q syndrome

C.

Idiopathic aplastic anaemia

D.

Acute myeloid leukaemia

E.

Inherited aplastic anaemia

F.

Myelofibrosis

G.

Refractory cytopenia with multilineage dysplasia

H.

Juvenile myelomonocytic leukaemia

I.

Refractory anaemia with an excess of blasts

J.

Refractory anaemia

A

Refractory cytopenia with multilineage dysplasia

774
Q

A consultant grills you on a ward round: there is a patient with a WBC of 140 x109/L, Hb 12 g/dL, Platelet count 320 x109/L. She complains of tiredness, night sweats, fever and abdominal pain. Her spleen is markedly enlarged. Blood film shows blasts, neutrophils, basophils. How would you treat her?

A.

Pseudopolycythaemia

B.

Splenomegaly

C.

Haematocrit

D.

Hydroxycarbamide

E.

Idiopathic myelofibrosis

F.

Erythropoeitin

G.

Venesection

H.

Chlorambucil

I.

Acute myeloid leukaemia

J.

Chronic myeloid leukaemia

K.

Polycythaemia vera

L.

Imitanib

M.

Essential thrombocythaemia

N.

Melphalan

O.

Tear drop poikilocytes

P.

Microcytosis

A

Imatinib

775
Q

You are asked to see a 76 year old man on the wards, who presented with fatigue, dyspnoea, bleeding gums and nightsweats. His abdomen is massively enlarged. You read his notes and find ‘bone marrow aspirate: ‘dry tap’. What would you expect to see on the blood film?

A.

Pseudopolycythaemia

B.

Splenomegaly

C.

Haematocrit

D.

Hydroxycarbamide

E.

Idiopathic myelofibrosis

F.

Erythropoeitin

G.

Venesection

H.

Chlorambucil

I.

Acute myeloid leukaemia

J.

Chronic myeloid leukaemia

K.

Polycythaemia vera

L.

Imitanib

M.

Essential thrombocythaemia

N.

Melphalan

O.

Tear drop poikilocytes

P.

Microcytosis

A

Tear drop poikilocytes

776
Q

A 55 year old female has a past medical history of deep vein thrombosis. She also complains of easy bruising. Her platelet count is 770 x109/L, CRP is 4mg/L. You prescribe aspirin.

A.

Pseudopolycythaemia

B.

Splenomegaly

C.

Haematocrit

D.

Hydroxycarbamide

E.

Idiopathic myelofibrosis

F.

Erythropoeitin

G.

Venesection

H.

Chlorambucil

I.

Acute myeloid leukaemia

J.

Chronic myeloid leukaemia

K.

Polycythaemia vera

L.

Imitanib

M.

Essential thrombocythaemia

N.

Melphalan

O.

Tear drop poikilocytes

P.

Microcytosis

A

Essential thrombocythaemia

777
Q

A routine medical of 33-year-old footballer reveals: Hb = 9.9g/dl and WCC = 130 x 109/L. His blood film shows whole spectrum of myeloid precursors, including a few blast cells. He admits to having frequent night sweats and blurred vision. There is a presence of Ph chromosome t(9;22) on cytogenetic analysis.

A.

Lung fibrosis

B.

Hairy cell leukaemia

C.

Hypothyroidism

D.

Septicaemia

E.

Acute promyelocytic leukaemia

F.

Chronic myeloid leukaemia

G.

Acute myeloid leukaemia

H.

Chronic lymphocytic leukaemia

I.

Bronchial carcinoma

J.

DIC

K.

Vincristine poisoning

L.

Tumour-lysis syndrome

M.

Richter’s syndrome

N.

Acute lymphoblastic leukaemia

A

CML

778
Q

A 5-year-old girl presents with failure to thrive, recurrent fever and bruising. Immunotyping reveals the presence of CD10..

A.

Lung fibrosis

B.

Hairy cell leukaemia

C.

Hypothyroidism

D.

Septicaemia

E.

Acute promyelocytic leukaemia

F.

Chronic myeloid leukaemia

G.

Acute myeloid leukaemia

H.

Chronic lymphocytic leukaemia

I.

Bronchial carcinoma

J.

DIC

K.

Vincristine poisoning

L.

Tumour-lysis syndrome

M.

Richter’s syndrome

N.

Acute lymphoblastic leukaemia

A

ALL

779
Q

The commonest adult leukaemia.

A

CLL

780
Q

50yr old man presents to his GP complaining of weight loss, tiredness, easy bruising and a painful big toe. On examination his spleen is massively enlarged. Investigation shows a raised serum urate. The peripheral blood film is abnormal, showing proliferation of which type of cell?

A.

Neutrophils

B.

Chromosome 9;22 translocation

C.

Spherocytes

D.

Pelger-Huet cells

E.

Blast cells

F.

Auer rods

G.

Eosinophils

H.

Reticulocytes

I.

Platelets

J.

Chromosome 11q23 deletion

K.

Clonal B lymphocytes

A

Neutrophils

CML. Increased mass of turning-over cells generates urate

781
Q

A 70yr old man complains of a year’s history of fatigue, weight loss and recurrent sinusitis. His white cell count is raised with a lymphocytosis of 283x109 /L. Blood film shows features of haemolysis and Coomb’s test is positive. Further investigation show the bone marrow, blood and lymph nodes are infiltrated with which cell population?

A.

Neutrophils

B.

Chromosome 9;22 translocation

C.

Spherocytes

D.

Pelger-Huet cells

E.

Blast cells

F.

Auer rods

G.

Eosinophils

H.

Reticulocytes

I.

Platelets

J.

Chromosome 11q23 deletion

K.

Clonal B lymphocytes

A

Clonal B lymphocytes

CLL. Only two chronic B cell leukaemia/lymphomas are CD5+: CLL (CD5+ CD23+) and Mantle Cell Lymphoma (CD5+ CD23-). CLL may be assoc. with Coombs positive AIHA and ITP. The combination is called Evans syndrome.

782
Q

What is a poor prognositc sign in CLL

A

del 11q23

783
Q

What differntiates between CML and myelodproliferative disorders and infections

A

Neutrophil ALP is low in CML

Raised in myeloproliferative disorders and infections

784
Q

What is the blast threshold in the BM for AML

A

20%

785
Q

characterized by less than 5% primitive blood cells (myeloblasts) in the bone marrow and pathological abnormalities primarily seen in red cell precursors

A

Refractory anemia (RA)

786
Q

characterized by less than 5% myeloblasts in the bone marrow, but distinguished by the presence of 15% or greater red cell precursors in the marrow being abnormal iron-stuffed cells called ‘ringed sideroblasts’

A

Refractory anemia with ringed sideroblasts (RARS)

787
Q

characterized by 5-19% myeloblasts in the marrow

A

Refractory anemia with excess blasts (RAEB)

788
Q

haracterized by 20-29% myeloblasts in the marrow (30% blasts is defined as acute myeloid leukemia in FAB classification but 20% in the WHO classification.. …therefore a controversial category and the WHO have abandoned teh RAEB-T category!)

A

Refractory anemia with excess blasts in transformation (RAEB-T)

789
Q

characterized by less than 20% myeloblasts in the bone marrow and greater than 1000 * 109/uL monocytes circulating in the peripheral blood. Also something that often comes up in exams: - syndrome, typically seen in older women with normal or high platelet counts and isolated deletions of the long arm of chromosome 5 in bone marrow cells.

A

Chronic myelomonocytic leukemia (CMML) - not to be confused with chronic myelogenous leukemia or CML

790
Q

Female Age at diagnosis: 74 years Transfusion-dependent anemia Normal or increased platelet counts along with bone marrow hyperplasia of hypolobulated micromegakaryocytes

A

q syndrome, there is a low incidence of thrombocytopenia. These patients may actually have thrombocytosis These patietnts have a low incidence of neutropenia, infection, and bleeding and low incidence of transformation into acute leukemi

791
Q

Treatment of 5q sunydrome

A

Lenalidomide

792
Q

A 44 year old with recurrent URTI and haematuria in last 6 months presents to GP. He also has a number of mouth ulcers and blood film demonstrates pancytopenia. What treatment would be appropriate? Options Androgen Anti-thymocyte globulin BMT Blood transfusion Corticosteroids Oral Iron Vitamin B12 ANS:Anti-thymocyte globulin I understand this is AA but I’m not quite sure when you would use the different treatment options e.g. corticosteroids, BMT, androgens….

A

This is covered very well in the lecture you have been given, but essentially - when supportive measures fail, Immune suppression is especially useful if a matched sibling donor for BMT is not available or if the patient is older than 60 years. Bone MArrow transplantation -HLA-matched sibling-donor BMT is the treatment of choice for a young patient with SAA (controversial but generally accepted for age <60 y). There are no hard and fast rules, and remember that that the cause of aplastic anaemia needs to be elucidated, and treatment may be directed specifically towards the underlying cause.

793
Q

An 83 year old woman presents to the A+E Departments with severe weakness and shortness of breath on minimal exertion. On examination, masses are felt in both left and right upper quadrants of the abdomen.

A

Myelofibrosis

794
Q

If thrombin time is up

A

there is a fibrinogen problem.

795
Q

If APTT or PT is up

A

there is a coagulation factor dysfunction or deficiency.

796
Q

If bleeding time is up

A

there is a platelet dysfunction or deficiency.

797
Q

To diagnose DIC you need

A

need low platelets, low fibrinogen, raised APTT and PT, raised D-dimers, schistocytes on blood smear, and a compatible clinical setting.

798
Q

“A 37 year old mother of 4 children, presents to her GP because of recurrent nose bleeds and feeling tired all the time and heavy periods.” Why is this osler weber rendu syndrome and not von willebrand disease?

A

The key to the question is “mother of 4 children” - vWD would almost certainly have been picked up due to prolonged bleeding during one of these pregnancies/deliveries. OWR is diagnosed by the triad of epistaxis, telangiectasia and a suitable family history. So whilst telangiectasia are not directly mentioned in the question, nosebleeds would suggest OWR as a possibility. As bleeding in OWR is from vascular malformations (caused by mutations in the TGF-B pathway) and not a direct coagulation defect, it would be less likely to be picked up on routine screening in pregnancy. This makes it a better fit in this question than vWD. The only documented associations between OWR and heavy menstrual bleeding are a few case reports suggesting uterine arterio-venous malformations. However this is a very common symptom in the normal population, and many OWR patients will have heavy periods with no relevance to their underlying disease process. The question could be more direct in pointing to OWR, but there is a widely varying phenotype and this is a very possible presentation. In real life you would perform a coagulation screen, take a good family history and you would have the diagnosis.

799
Q

Why is Warfarin always started under Heparin cover

A

Warfarin alone initially increases the clotting risk because proteins C and S (the anticoagulant proteins) have shorter half lives and disappear from the blood faster than factors II, VII, IX, X (the procoagulant proteins).

800
Q

How can Heparin induced thrombcotyopaenia be classified

A

Types 1 and 2

801
Q

Type 1 HIT

A

Dose related effect mediated by platelet aggregation

802
Q

Type 2 HIT

A

Unpredictable immune response with antibodies directed against the heparin-platelet factor 4 complex

Large aggregates cause thrombosis

803
Q

Treatment of HIT T2

A

Stop heparin and start a direct thrombin inhibiotr e.g. hirudin

804
Q

Which treatment does HIT more commonly following

A

UFH

805
Q

What is the exception to usual rule that Warfarin is more effective than LMWH?

A

Cancer

806
Q

Gaucher’s disease

A

a hereditary disease in which the metabolism and storage of fats is abnormal. It results in bone fragility, neurological disturbance, anaemia, and enlargement of the liver and spleen.

807
Q

Spur cell hemolytic anemia

A

Spur cell hemolytic anemia, is a form of hemolytic anemia that results secondary to severe impaired liver function or cirrhosis. Chronic liver disease impairs the liver’s ability to esterify cholesterol, causing free cholesterol to bind to the red cell membrane, increasing its surface area. This condition also creates rough or thorny projections on the erythrocyte named acanthocytes. [

808
Q

A 10 year old boy presenting with tan-to-grey hyperpigmented patches on his upper trunk, neck and face, nail ridges and leukoplakia.

A.

Dyskeratosis congenita

B.

Hepatitis C infection

C.

Parvovirus B19 infection

D.

Aplastic anaemia

E.

Fanconi anaemia

F.

Myelofibrosis

G.

Drug-induced

H.

Radiation-induced

I.

Acute myeloid leukaemia

J.

Systemic lupus erythematosus

A

Dyskeratosis congenita is characterised by a triad of Nail dystrophy, leukoplakia and cutaneous manifestations.

809
Q

A 76 year old man presents to his GP with increasing tiredness, weakness and a long-standing cold. The blood results ordered by the GP showed that the gentleman was anaemic and that increased blast cells were present.

A.

Dyskeratosis congenita

B.

Hepatitis C infection

C.

Parvovirus B19 infection

D.

Aplastic anaemia

E.

Fanconi anaemia

F.

Myelofibrosis

G.

Drug-induced

H.

Radiation-induced

I.

Acute myeloid leukaemia

J.

Systemic lupus erythematosus

A

AML

810
Q

An 83 year old woman presents to the A&E Departments with severe weakness and shortness of breath on minimal exertion. On examination, masses are felt in both left and right upper quadrants of the abdomen. Blood film show leukoerythroblastic cells and teardrop poikilocytes.

A.

Dyskeratosis congenita

B.

Hepatitis C infection

C.

Parvovirus B19 infection

D.

Aplastic anaemia

E.

Fanconi anaemia

F.

Myelofibrosis

G.

Drug-induced

H.

Radiation-induced

I.

Acute myeloid leukaemia

J.

Systemic lupus erythematosus

A

Myelofibrosis

811
Q

A 19 year old Jewish male presenting with multiple pathological fractures and hypersplenism.

A.

Paroxysmal nocturnal haemoglobinuria

B.

Sepsis

C.

Autoimmune haemolytic anaemia

D.

Pyruvate kinase deficiency

E.

Hereditary spherocytosis

F.

Sickle-cell disease

G.

Cardiac haemolysis

H.

Spur cell anaemia

I.

Drug-induced immune haemolysis

J.

Gaucher’s disease (glucosylceramide lipidosis)

K.

Hereditary elliptocytosis

L.

Haemolytic uraemic syndrome

A

Gaucher’s

812
Q

A 26 year old primary school teacher presents with chronic anaemia. She has an increased (unconguated) bilirubin, and has had well controlled systemic lupus erythematosus for 7 years.

A.

Paroxysmal nocturnal haemoglobinuria

B.

Sepsis

C.

Autoimmune haemolytic anaemia

D.

Pyruvate kinase deficiency

E.

Hereditary spherocytosis

F.

Sickle-cell disease

G.

Cardiac haemolysis

H.

Spur cell anaemia

I.

Drug-induced immune haemolysis

J.

Gaucher’s disease (glucosylceramide lipidosis)

K.

Hereditary elliptocytosis

L.

Haemolytic uraemic syndrome

A

AIHA

813
Q

A 35 year old women complains of abdominal pain. There is associated pancytopenia, and a Ham’s test is positive.

A.

Paroxysmal nocturnal haemoglobinuria

B.

Sepsis

C.

Autoimmune haemolytic anaemia

D.

Pyruvate kinase deficiency

E.

Hereditary spherocytosis

F.

Sickle-cell disease

G.

Cardiac haemolysis

H.

Spur cell anaemia

I.

Drug-induced immune haemolysis

J.

Gaucher’s disease (glucosylceramide lipidosis)

K.

Hereditary elliptocytosis

L.

Haemolytic uraemic syndrome

A

PNH

814
Q

A woman aged 69 with no past medical history except osteoarthritis suffered acute haemolysis after her right hip was replaced. There was no evidence of splenomegaly or lymphadenopathy and both warm and cold antibody tests were negative. When she had the left hip replaced 2 years later she again developed haemolysis soon after the anaesthetic. She was tested for IgG and IgE antibodies to the anaesthetic. Seven months later she had a revision arthroplasty and haemolysed again. Which condition might she have?

A.

Sickle cell anaemia

B.

Paroxysmal cold haemoglobinuria

C.

Primary autoimmune haemolytic anaemia

D.

Paroxysmal nocturnal haemoglobinuria

E.

Cephalosporin-induced haemolytic anaemia

F.

Hereditary elliptocytosis

G.

G6PD deficiency

H.

Autoimmune haemolytic anaemia due to infectious mononucleosis

I.

Hereditary spherocytosis

J.

Disseminated intravascular coagulation

K.

Sepsis

A

Cephalosporin-induced haemolytic anaemia

815
Q

In which condition might the sucrose and Ham acid haemolysis tests be positive?

A

PNH

816
Q

Mr RX came to Fulham from Thailand last year. He has inflammatory bowel disease and is taking dapsone for his dermatitis herpetiformis. Which of the above conditions would be likely and clinically relevant?

A.

Sickle cell anaemia

B.

Paroxysmal cold haemoglobinuria

C.

Primary autoimmune haemolytic anaemia

D.

Paroxysmal nocturnal haemoglobinuria

E.

Cephalosporin-induced haemolytic anaemia

F.

Hereditary elliptocytosis

G.

G6PD deficiency

H.

Autoimmune haemolytic anaemia due to infectious mononucleosis

I.

Hereditary spherocytosis

J.

Disseminated intravascular coagulation

K.

Sepsis

A

Dapsone is used to treat dermatitis herpetiformis. Dapsone is known to cause haemolysis in G6PD deficient patients, so it is avoided. G6PD deficiency in commoner in Thai people.

817
Q

A 29 year old man noticed he had yellow eyes and dark urine. He was always tired, and could not take part in sports as he easily became short of breath. There was no itching, fever or bleeding, and he was not taking any drugs. On examination he was anaemic, jaundiced, afebrile and had no palpable lymphadenopathy, hepatosplenomegaly or rash. His blood tests showed Hb 5.4g/Dl and raised WCC (40 x 109/L), bilirubin (47 µmol/l), aspartate transaminase (90iu/L) and lactate dehydrogenase (5721iu/l). The blood film showed polychromic nucleated red cells and spherocytes and the reticulocyte count was 9%. Direct Coombs’ test revealed IgG and C3 on the red cell surfaces. The serum contained a warm non-specific autoantibody (i.e. it reacted with all the red cells in the test panel). Antinuclear antibodies and rheumatoid factor tests were negative and immunoglobulin levels were normal; there were no paraprotein bands in his serum. He failed to respond to high-dose corticosteroids and had a splenectomy three weeks later.

A.

Sickle cell anaemia

B.

Paroxysmal cold haemoglobinuria

C.

Primary autoimmune haemolytic anaemia

D.

Paroxysmal nocturnal haemoglobinuria

E.

Cephalosporin-induced haemolytic anaemia

F.

Hereditary elliptocytosis

G.

G6PD deficiency

H.

Autoimmune haemolytic anaemia due to infectious mononucleosis

I.

Hereditary spherocytosis

J.

Disseminated intravascular coagulation

K.

Sepsis

A

Primary AIHA

818
Q

In which condition might a Donath-Landsteiner be positive?

A

Paroxysmal cold haemoglobinuria

819
Q

A 28 year old female presents with fever < 40 C and rigors approx. 1 ½ hours after transfusion. She has two children and previously had a blood transfusion 7 years ago.

A

Febrile non haemolytic transfusion reaction

Febrile non-haemolytic transfusion reaction (FNHTR) is an immediate reaction, causing fever and rigors. In contrast, delayed haemolytic transfusion reaction (DHTR) manifests days to weeks after a transfusion, acommpanied by a falling haemoglobin and jaundice or haemoglobinuria. Bacterial contamination can present in a similar manner to FNHTR but is differentiated by a much more marked fever; in addition, profound hypotension and tachycardia may occur.

820
Q

A 44 year old male develops a pyrexia of >40 C and marked hypotension very shortly after receiving a blood transfusion. He has never had a transfusion before and there is no evidence of ABO blood group / rhesus incompatibility.

A.

Anaphylactic reaction

B.

Fluid overload

C.

TRALI

D.

Graft versus host disease

E.

Bacterial contamination

F.

Delayed haemolytic transfusion reaction.

G.

Viral contamination

H.

Allergic reaction

I.

Febrile non haemolytic transfusion reaction

J.

Immediate haemolytic transfusion reaction

K.

Iron overload

A

Bacterial contamination

821
Q

n 18 year old boy with sickle cell anaemia is observed to have short stature. Further tests reveal poor cardiac function

A.

Anaphylactic reaction

B.

Fluid overload

C.

TRALI

D.

Graft versus host disease

E.

Bacterial contamination

F.

Delayed haemolytic transfusion reaction.

G.

Viral contamination

H.

Allergic reaction

I.

Febrile non haemolytic transfusion reaction

J.

Immediate haemolytic transfusion reaction

K.

Iron overload

A

Fe overload

822
Q

An 18 year old African girl known to suffer from sickle cell anaemia develops a fever, sudden lethargy, pallor and arthralgia two months post-transfusion. Investigations reveal bone marrow red cell aplasia and a positive Paul-Bunnell test.

A.

CMV infection

B.

Post-transfusion purpura (PTP)

C.

Immunological haemolytic reaction

D.

Non-haemolytic reaction

E.

Delayed haemolytic transfusion reaction (DHTR)

F.

Transfusion-related acute lung injury (TRALI)

G.

Allergic reaction to transfusion

H.

Graft vs. Host disease (GvHD)

I.

Iron overload

J.

Reaction to massive transfusion

K.

Air embolism

L.

Transfusion-related fluid overload

M.

B19 parvovirus infection

A

B19 parvovirus infection

823
Q

A 32 year old Irish man was noted to have a temperature of 36.9ºC and blood electrolyte results of: urea = 5.2 mmol/L, sodium = 144 mmol/L, potassium = 5.5 mmol/L, calcium = 2.5 mmol/L after receiving 10 units of blood over a 24 hour period.

A.

CMV infection

B.

Post-transfusion purpura (PTP)

C.

Immunological haemolytic reaction

D.

Non-haemolytic reaction

E.

Delayed haemolytic transfusion reaction (DHTR)

F.

Transfusion-related acute lung injury (TRALI)

G.

Allergic reaction to transfusion

H.

Graft vs. Host disease (GvHD)

I.

Iron overload

J.

Reaction to massive transfusion

K.

Air embolism

L.

Transfusion-related fluid overload

M.

B19 parvovirus infectio

A

Reaction to massive transfusion

824
Q

A 55 year old British female developed an itchy, diffuse erythematous rash on both arms fifteen minutes after receiving a blood transfusion. This rash responded well to acrivastine.

A.

CMV infection

B.

Post-transfusion purpura (PTP)

C.

Immunological haemolytic reaction

D.

Non-haemolytic reaction

E.

Delayed haemolytic transfusion reaction (DHTR)

F.

Transfusion-related acute lung injury (TRALI)

G.

Allergic reaction to transfusion

H.

Graft vs. Host disease (GvHD)

I.

Iron overload

J.

Reaction to massive transfusion

K.

Air embolism

L.

Transfusion-related fluid overload

M.

B19 parvovirus infection

A

Allergic reaction to transfusion

825
Q

Patient develops shortness of breath, dry cough and chills. Donors blood was found to contain anti-leucocyte antibodies with similar specificity to the patient’s white blood cell antigens.

A.

Iron overload

B.

TA-GVHD – Transfusion associated graft versus host disease

C.

Bacterial infection

D.

ABO incompatible

E.

DHTR – Delayed Haemolytic transfusion reaction

F.

IgA deficiency

G.

FNHTR – Febrile non-haemolytic transfusion reaction

H.

TRALI – Transfusion related acute lung injury

I.

Urticarial rash

A

TRALI

826
Q

Patient has a severe anaphylactic reaction soon after transfusion. Signs and symptoms include wheeze, raised pulse, low blood pressure and laryngeal oedema.

A.

Iron overload

B.

TA-GVHD – Transfusion associated graft versus host disease

C.

Bacterial infection

D.

ABO incompatible

E.

DHTR – Delayed Haemolytic transfusion reaction

F.

IgA deficiency

G.

FNHTR – Febrile non-haemolytic transfusion reaction

H.

TRALI – Transfusion related acute lung injury

I.

Urticarial rash

A

IgA deficiency

827
Q

A 40 year old male patient with known Sickle-Cell anaemia develops mild symptoms of fever and rigors 3 to 4 days after a transfusion.

A.

Transfursion related acute lung injury

B.

CMV infection

C.

Anaphylaxis due to IgA deficiency

D.

Delayed transfusion reaction

E.

Febrile non-haemolytic transfusion reaction

F.

Post-transfusion purpura

G.

Air embolism

H.

Iron overload

I.

ABO incompatible

J.

Graft vs host disease

K.

Urticarial rash

L.

Bacterial infection

A

Febrile non-haemolytic transfusion reaction

828
Q

A 24 year old male who was diagnosed with thalassaemia major at 13 months presents to outpatients clinic complaining of malaise and erectile dysfunction.

A.

Delayed haemolytic transfusion reaction (DHTR)

B.

Kleihauer test

C.

Viral contamination of transfusion

D.

Pulmonary embolism

E.

Guthrie test

F.

Bacterial contamination of transfusion

G.

Immediate haemolytic transfusion reaction

H.

Transfusion haemosiderosis

I.

Transfusion-related acute lung injury (TRALI)

J.

Allergic reaction to forein protein in donor blood

A

Transfusion haemosiderosis

829
Q

A 25 year old man vomits and becomes restless on receiving a blood transfusion, he also complains of chest and abdominal pain.

A.

TRALI

B.

Post-transfusion purpura

C.

Delayed haemolytic transfusion reaction

D.

Fungal infection

E.

Pulmonary Embolism

F.

Iatrogenic Iron overload

G.

Allergic reaction

H.

Bacterial infection

I.

Viral infection

J.

Immediate haemolytic transfusion reaction

K.

Transfusion-associated graft versus host disease

L.

Massive transfusion reaction

M.

Air Embolism

A

Immediate haemolytic transfusion reaction

830
Q

A 60 year old man who has been given a blood transfusion has noticed an itchy rash on his arms and legs.

A.

TRALI

B.

Post-transfusion purpura

C.

Delayed haemolytic transfusion reaction

D.

Fungal infection

E.

Pulmonary Embolism

F.

Iatrogenic Iron overload

G.

Allergic reaction

H.

Bacterial infection

I.

Viral infection

J.

Immediate haemolytic transfusion reaction

K.

Transfusion-associated graft versus host disease

L.

Massive transfusion reaction

M.

Air Embolism

A

Allergic reaction

831
Q

Pathophysiology of FNHTR

A

FNHTR is thought to be caused by the reaction between leukocyte antibodies present in the plasma of a recipient reacting against leukocytes present in transfused (donor) red cells. However, platelet associated FNHTR seems to be related to the presence of pyrogenic cytokines released from leukocytes during the platelet storage. Leukoreduction (i.e. removal of white cells prior to transfusion) of the cellular blood components may effectively reduce the occurrence of FNHTR.

832
Q

Difference between TRALI and TA-GvD

A

TRALI occurs if the donor’s plasma contains white cell antibodies incompatible with the recipient’s white cells. TRALI is characterised by chills, fever, dry cough and breathlessness with cardiac failure. TA-GvD is a rare complication in which donor T lymphocytes mount a response against the recipient’s lymphoid tissue. Typical symptoms include fever and erythematous macular papular rash. Other symptoms include cough, abdominal pain, vomiting and profuse diarrhoea.

833
Q

Which Ab mediates cold autoimmune haemolysis

A

IgM

834
Q

What can lead to cold-Ab mediated haemolysis

A

May be polycolonal and arise as a result of infection e.g. mycoplasma pneumonia or infectious mononucleosis

It can also be monoclonal, secondary to lymphoma

835
Q

Pathophysiology of cold AIHA

A

In COLD-antibody mediated haemolysis, the Ab (usually IgM) may be polyclonal and arise as a result of infection (e.g mycoplasma pneumonia or infectious mononucleosis) or may be monoclonal secondary to a lymphoproliferative disorder (e.g. Non-Hodgekins Lymphoma). The red cells become coated with IgM antibodies in the cooler peripheral circulation. Complement is activated at slightly higher temperatures, resulting in intravascular haemolysis. IgM is detectable on the red cells at 4 deg C. At higher temperatures, IgM detaches from the red cell surface but complement can still be detected. Circulating free cold autoantibodies - cold agglutins - are also present in the patients serum. A direct Coombs’ test may be positive for complement (but not for antibodies, as the IgM antibodies elute from the red cell into the serum in vitro). In addition to cold avoidance, other Rx options include drugs such as chlorambucil.

836
Q

Which Abs are associated with warma AIHA

A

IgG

837
Q

With what conditions is warm AIHA associated?

A

0% of cases are idiopathic, but other associations include autoimmune diseases eg. SLE, or drugs.

838
Q

Pathophysiology of warm AIHA

A

WARM autoimmune haemolytic anaemias are associated with IgG antibodies to red blood cells. These antibodies react best at body temperature. 50% of cases are idiopathic, but other associations include autoimmune diseases eg. SLE, or drugs. Red cells are opsonised with either antibody alone, or antibody and complement components, and subsequently removed by splenic macrophages. The patient’s red cells are direct Coombs’ test positive; they promptly agglutinate when mixed with antiglobulin reagent. Rx may be steroids or splenectomy.

839
Q

How does PRV cause a low ferritin

A

the Hb, WBC and platelet counts would be raised together with a low ferritin. Ferritin falls because of the increased demand for iron due to increased haematopoesis.

840
Q

An 18 year old African girl known to suffer from sickle cell anaemia develops a fever, sudden lethargy, pallor and arthralgia two months post-transfusion. Investigations reveal bone marrow red cell aplasia and a positive Paul-Bunnell test.

A

infection with erythrovirus (parvovirus) B19 may result in a false positive Paul Bunnell test’. PS. The red cell aplasia with haemoglobinopathy gives it away that its Parvovirus B19. Normally, we would mount a reticulocyte response and be assymptomatic (or slapped cheek in children), but sickle cell = reduced red cell lifespan, reticulocytopenia and marrow aplasia = crisis!!

841
Q

Found in patients with Myeloma with low serum albumin and oedema.

A.

Bence-Jones proteins

B.

Extramedullary tumour deposits

C.

Paraprotein

D.

Amyloid

E.

Inflammation

F.

Osteoblasts

G.

Barry-Jane proteins

H.

Osteoclasts

A

Amyloid

842
Q

Misfolded protein deposited in myeloma-associated amyloidosis

A.

Interferon α + ibuprofen

B.

Lenalidomide + low dose dexamethasone

C.

Melphalan + prednisolone

D.

Infliximab + budesonide

E.

Monoclonal gammopathy of undetermined significance (MGUS)

F.

AL amyloid

G.

IgM

H.

Multiple myeloma

I.

Thalidomide + high dose dexamethasone

J.

Bortezomib

K.

Rituximab

L.

Waldenstrom’s macroglobinaemia

M.

AA amyloid

N.

Aβ amyloid

O.

Anaemia & renal failure

A

AL amyloid

843
Q

How can treatment of myeloma be categroised

A

Into those sutiable for auto-SCT and those who are not

844
Q

Treatment of a patient with MM unsuitable for auto-SCT

A

Melphalan + Pred + thalidomide= first line

Melphalan + pred + bortezomib= second line ( can’t tolerate thalidomide)

845
Q

Treatment of MM in patient sutiable for SCT

A

Use induction chemo:

Lenalidomide + Dex =first line

Bortezomib + dex= second line

Alkylating agents e.g. mephalan are best avoided for induction chemo as they may compromise SC reserve

846
Q

Asymptomatic, serum monoclonal protein 10g/L, marrow plasma cells 15%, serum Ca 2.3 mmol/L, estimated GFR 30 mL/min, Hb 8 g/dL, lytic vertebral lesions

A.

Primary hyperparathyroidism

B.

Waldenstrom’s macroglobulinaemia

C.

MGUS

D.

Sarcoidosis

E.

Solitary plasmacytoma of bone (SPB)

F.

Metastatic breast cancer

G.

Primary amyloidosis

H.

Secondary hyperparathyroidism

I.

CLL

J.

Multiple myeloma

K.

Smouldering multiple myeloma

A

MM

847
Q

Previously fit 35yo Afro Carribean female, sudden onset back pain, no history of trauma, 1 month history polyuria, urine specific gravity raised but dipstick negative for protein (and normal in all other respects), estimated GFR 70mL/min, vertebral fracture and bilateral femoral neck fractures on radiograph

A.

Primary hyperparathyroidism

B.

Waldenstrom’s macroglobulinaemia

C.

MGUS

D.

Sarcoidosis

E.

Solitary plasmacytoma of bone (SPB)

F.

Metastatic breast cancer

G.

Primary amyloidosis

H.

Secondary hyperparathyroidism

I.

CLL

J.

Multiple myeloma

K.

Smouldering multiple myeloma

.

A

MM

848
Q

Asymptomatic, serum monoclonal protein 25g/L, marrow plasma cells 5%, serum Ca 2.3 mmol/L, estimated GFR 100mL/min, Hb 12.5 g/dL, skeletal survey normal

A.

Primary hyperparathyroidism

B.

Waldenstrom’s macroglobulinaemia

C.

MGUS

D.

Sarcoidosis

E.

Solitary plasmacytoma of bone (SPB)

F.

Metastatic breast cancer

G.

Primary amyloidosis

H.

Secondary hyperparathyroidism

I.

CLL

J.

Multiple myeloma

K.

Smouldering multiple myeloma

A

MGUS

849
Q

Asymptomatic, serum monoclonal protein 30g/L, marrow plasma cells 10%, serum Ca 2.3 mmol/L, estimated GFR 100mL/min, Hb 12.5 g/dL, skeletal survey normal

A.

Primary hyperparathyroidism

B.

Waldenstrom’s macroglobulinaemia

C.

MGUS

D.

Sarcoidosis

E.

Solitary plasmacytoma of bone (SPB)

F.

Metastatic breast cancer

G.

Primary amyloidosis

H.

Secondary hyperparathyroidism

I.

CLL

J.

Multiple myeloma

K.

Smouldering multiple myeloma

A

Smouldering multiple myeloma

850
Q

Which paraprotein is most commonly raised in patients with multiple myeloma?

A

IgG

851
Q

Which cytokine is an important growth factor in the development of myeloma?

A

IL-6

852
Q

Elevated levels imply a poor prognosis in myeloma patients

A

Beta a2 microglobulin

853
Q

How is MM staged

A

Using the international staging system

Uses beta 2 microglobulin and albumin to stage a patient’s disease

Age and cytogenetics are the only other factors that impact on Px

854
Q

A 65 yr old man presents to his GP with general malaise, weight loss and visual disturbances that he likens to looking through a watery car windscreen. On examination he has peripheral lymph node enlargement. Protein electrophoresis shows an IgM paraprotein.

A.

Metastatic carcinoma

B.

Multiple myeloma

C.

Monoclonal gammopathy of undetermined significance

D.

Chronic lymphocytic leukaemia

E.

Secondary amyloidosis

F.

Waldenstrom’s macroglobulinaemia

G.

Primary amyloidosis

A

Waldenstrom’s macroglobulinaemia is a malignant disease of B cells which are lymphoplasmacytoid in appearance. These cells secrete IgM paraprotein which gives rise to clinical manifestations. The disease is commonly seen in elderly men. It is an indolent disease with a median survival of 3 to 5 years, but some patients may survive 10 years or longer. It is regarded as a low grade non-Hodgkin’s lymphoma.

855
Q

A 49-year-old woman presented with a 6-month history of vague aches and pains in her chest. On examination, she was overweight but had no abnormal physical signs. Protein electrophoresis showed a small paraprotein band in the gamma region; this band was an IgG of lambda type. A bone marrow biopsy showed only 12% plasma cells. There was no protein in her urine.

A.

Non-Hodgkin’s lymphoma

B.

Hairy cell leukaemia

C.

Sarcoidosis

D.

Acute leukaemia

E.

Multiple myeloma

F.

Hodgkin’s lymphoma

G.

Bone metastasis

H.

Fractured vertebrae

I.

Sezary syndrome

J.

Benign paraproteinaemia

A

Benign paraproteinaemia

856
Q

A 71-year-old man presented with sharp, constant, low back pain, dating from a fall from a ladder 6 weeks earlier. He admitted to vague malaise for over 8 months. He had a raised serum calcium level (3.2mmol/l) but a normal alkaline phosphatase. X-rays of his back showed a small, punched-out lesion in the second lumbar vertebra and a Bone marrow biopsy showed an increased number of atypical plasma cells; these constituted 45% of the nucleated cells found on the film.

A.

Non-Hodgkin’s lymphoma

B.

Hairy cell leukaemia

C.

Sarcoidosis

D.

Acute leukaemia

E.

Multiple myeloma

F.

Hodgkin’s lymphoma

G.

Bone metastasis

H.

Fractured vertebrae

I.

Sezary syndrome

J.

Benign paraproteinaemia

A

Multiple myeloma

857
Q

A 43 year old man presents to his GP with concerns over a tender lump on the left side of his abdomen. Investigation showed a normal haemoglobin but a mildly raised white-cell count (13.2 x 109/l). On the blood film these cells were mainly small mononuclear cells resembling lymphocytes. These cells stained positively for tartrate-resistant acid phosphatase.

A.

Non-Hodgkin’s lymphoma

B.

Hairy cell leukaemia

C.

Sarcoidosis

D.

Acute leukaemia

E.

Multiple myeloma

F.

Hodgkin’s lymphoma

G.

Bone metastasis

H.

Fractured vertebrae

I.

Sezary syndrome

J.

Benign paraproteinaemia

A

Hairy cell leukaemia

858
Q

A 69 year old man presents with a complaint of right elbow pain. Radiography shows a lytic lesion in the area of the right proximal radius. Biopsy of the lesion reveals a mono-clonal population of plasma cells consistent with a plasmacytoma. A radiographic skeletal bone survey shows other similar lesions.

A.

Non-Hodgkin’s lymphoma

B.

Hairy cell leukaemia

C.

Sarcoidosis

D.

Acute leukaemia

E.

Multiple myeloma

F.

Hodgkin’s lymphoma

G.

Bone metastasis

H.

Fractured vertebrae

I.

Sezary syndrome

J.

Benign paraproteinaemia

A

MM

859
Q

Corticosteroid refractory haemolytic anaemia

A

Splenectomy

860
Q

Chronic lymphocytic leukaemia

A.

Folate

B.

Thymectomy

C.

Splenectomy

D.

Lenalidomide (Revlimid) and low dose dexamethasone followed by autologous stem cell transplant (SCT)

E.

Anagrelide

F.

Campath (anti CD52, alemtuzumab)

G.

Imatinib

H.

Regular surveillance but no active treatment

I.

Bortezomib (Velcade)

J.

Venesection and aspirin

K.

Hydroxyurea

L.

Rituximab (anti CD20)

M.

Leucovorin (Folinic acid, Formyl tetrahydrofolate)

N.

Treatment with anti lymphocyte globulin

O.

Cyclophosphamide, fludarabine and rituximab

P.

Dexamethasone alone

Q.

Lenalidomide (Revlimid) and low dose dexamethasone followed by allogeneic stem cell transplant (SCT)

R.

Thalidomide and dexamethasone

S.

Melphalan

A

Cyclophosphamide, fludarabine and rituximab

861
Q

Chronic myeloid leukaemia (also known as chronic granulocytic leukaemia)

A.

Folate

B.

Thymectomy

C.

Splenectomy

D.

Lenalidomide (Revlimid) and low dose dexamethasone followed by autologous stem cell transplant (SCT)

E.

Anagrelide

F.

Campath (anti CD52, alemtuzumab)

G.

Imatinib

H.

Regular surveillance but no active treatment

I.

Bortezomib (Velcade)

J.

Venesection and aspirin

K.

Hydroxyurea

L.

Rituximab (anti CD20)

M.

Leucovorin (Folinic acid, Formyl tetrahydrofolate)

N.

Treatment with anti lymphocyte globulin

O.

Cyclophosphamide, fludarabine and rituximab

P.

Dexamethasone alone

Q.

Lenalidomide (Revlimid) and low dose dexamethasone followed by allogeneic stem cell transplant (SCT)

R.

Thalidomide and dexamethasone

S.

Melphalan

A

Imatinib

862
Q

Multiple myeloma

A.

Folate

B.

Thymectomy

C.

Splenectomy

D.

Lenalidomide (Revlimid) and low dose dexamethasone followed by autologous stem cell transplant (SCT)

E.

Anagrelide

F.

Campath (anti CD52, alemtuzumab)

G.

Imatinib

H.

Regular surveillance but no active treatment

I.

Bortezomib (Velcade)

J.

Venesection and aspirin

K.

Hydroxyurea

L.

Rituximab (anti CD20)

M.

Leucovorin (Folinic acid, Formyl tetrahydrofolate)

N.

Treatment with anti lymphocyte globulin

O.

Cyclophosphamide, fludarabine and rituximab

P.

Dexamethasone alone

Q.

Lenalidomide (Revlimid) and low dose dexamethasone followed by allogeneic stem cell transplant (SCT)

R.

Thalidomide and dexamethasone

S.

Melphalan

A

Lenalidomide (Revlimid) and low dose dexamethasone followed by autologous stem cell transplant (SCT)

863
Q

Treatment of MGUS and smouldering myeloma

A

Regular surveillance but no active treatment

864
Q

Used in solid organ transplantation, multiple sclerosis, NHL. Depletes lymphocytes. Side effects include ITP and Graves disease.

A.

Folate

B.

Thymectomy

C.

Splenectomy

D.

Lenalidomide (Revlimid) and low dose dexamethasone followed by autologous stem cell transplant (SCT)

E.

Anagrelide

F.

Campath (anti CD52, alemtuzumab)

G.

Imatinib

H.

Regular surveillance but no active treatment

I.

Bortezomib (Velcade)

J.

Venesection and aspirin

K.

Hydroxyurea

L.

Rituximab (anti CD20)

M.

Leucovorin (Folinic acid, Formyl tetrahydrofolate)

N.

Treatment with anti lymphocyte globulin

O.

Cyclophosphamide, fludarabine and rituximab

P.

Dexamethasone alone

Q.

Lenalidomide (Revlimid) and low dose dexamethasone followed by allogeneic stem cell transplant (SCT)

R.

Thalidomide and dexamethasone

S.

Melphalan

A

Campath (anti CD52, alemtuzumab)

865
Q

Add-on anti-proteasome drug for myeloma

A

Bortezomib (Velcade)

866
Q

Anti-proliferative used in polycythaemia rubra vera and essential thrombocythaemia

A

Hydroxyurea

867
Q

Reduces platelet count in thrombocythaemia but causes palpitations, tachycardia, fluid retention

A

Anagrelide

868
Q

Standard prophylaxis accompanying a once weekly myelosuppressant when used in rheumatoid arthritis

A

Folate

869
Q

Rescue drug after high dose methotrexate is used for gestational trophoblastic disease or intrathecal ALL

A

Leucovorin (Folinic acid, Formyl tetrahydrofolate)

870
Q

Used in solid organ transplantation, multiple sclerosis, NHL. Depletes B lymphocytes more than T lymphocytes.

A.

Folate

B.

Thymectomy

C.

Splenectomy

D.

Lenalidomide (Revlimid) and low dose dexamethasone followed by autologous stem cell transplant (SCT)

E.

Anagrelide

F.

Campath (anti CD52, alemtuzumab)

G.

Imatinib

H.

Regular surveillance but no active treatment

I.

Bortezomib (Velcade)

J.

Venesection and aspirin

K.

Hydroxyurea

L.

Rituximab (anti CD20)

M.

Leucovorin (Folinic acid, Formyl tetrahydrofolate)

N.

Treatment with anti lymphocyte globulin

O.

Cyclophosphamide, fludarabine and rituximab

P.

Dexamethasone alone

Q.

Lenalidomide (Revlimid) and low dose dexamethasone followed by allogeneic stem cell transplant (SCT)

R.

Thalidomide and dexamethasone

S.

Melphalan

A

Rituximab (anti CD20)

871
Q

Myeloma

A.

Variable B cell

B.

Indolent B cell

C.

Aggressive B cell

D.

Variable T cell

E.

Aggressive T cell

F.

Indolent T cell

A

Variable B cell

872
Q

Most easily curable B cell neoplasm

A.

Variable B cell

B.

Indolent B cell

C.

Aggressive B cell

D.

Variable T cell

E.

Aggressive T cell

F.

Indolent T cell

A

Aggressive B cell

873
Q

Follicular lymphoma

A.

Variable B cell

B.

Indolent B cell

C.

Aggressive B cell

D.

Variable T cell

E.

Aggressive T cell

F.

Indolent T cell

A

Indolent B cell

874
Q

An elderly lady is found to suffer from Epstein-Barr virus. She is late noted to have splenic enlargement.

A.

Multiple Myeloma

B.

Hairy Cell Leukaemia

C.

Radiation Therapy Alone

D.

Aplastic Anaemia

E.

Chronic Lymphocytic Leukaemia

F.

Acute Myeloid Leukaemia

G.

Polycythaemia Rubra Vera

H.

Combination Chemotherapy

I.

ABVD combination chemotherapy + radiotherapy if required

J.

Hodgkins Stage IIA

K.

Myelodysplasia

L.

Hodgkins Disease Stage IB

M.

Burkitts Lymphoma

N.

Primary Amyloidosis

A

Burkitts Lymphoma

875
Q

Advanced Hodgkins disease should be treated with…..

A.

Multiple Myeloma

B.

Hairy Cell Leukaemia

C.

Radiation Therapy Alone

D.

Aplastic Anaemia

E.

Chronic Lymphocytic Leukaemia

F.

Acute Myeloid Leukaemia

G.

Polycythaemia Rubra Vera

H.

Combination Chemotherapy

I.

ABVD combination chemotherapy + radiotherapy if required

J.

Hodgkins Stage IIA

K.

Myelodysplasia

L.

Hodgkins Disease Stage IB

M.

Burkitts Lymphoma

N.

Primary Amyloidosis

A

Combination chemotherapy

876
Q

Pathological stage IA or IIA disease may be treated with……

A.

Multiple Myeloma

B.

Hairy Cell Leukaemia

C.

Radiation Therapy Alone

D.

Aplastic Anaemia

E.

Chronic Lymphocytic Leukaemia

F.

Acute Myeloid Leukaemia

G.

Polycythaemia Rubra Vera

H.

Combination Chemotherapy

I.

ABVD combination chemotherapy + radiotherapy if required

J.

Hodgkins Stage IIA

K.

Myelodysplasia

L.

Hodgkins Disease Stage IB

M.

Burkitts Lymphoma

N.

Primary Amyloidosis

A

ABVD combination chemotherapy + radiotherapy if required

is an oncogenic virus and may be associated with Burkitt’s Lymphoma and nasopharygeal carcinoma.

Q5: Treatment for Stage I + II Hodgkin’s Lymphoma used to be combined chemo + radiotherapy, but radiotherapy is dangerous in that it increases risk of secondary malignancies eg breast cancer and end-organ damage eg heart disease leading to deaths by MI, stroke, CHF. Reducing the field treated with radiotherapy reduces but does not eliminate these risks. One large review (DOI 10.1007/s11899-011-0088-8) says ‘Most young patients with non-bulky, localised, early-stage disease do extremely well on chemotherapy alone’. There are a number of trials currently looking at how to better identify the patients for whom the benefits of radiotherapy would out-weigh the risks.

877
Q

A subtype of Non-Hodgkin lymphoma associated with very aggressive disease.

A.

Night sweats

B.

Hodgkin lymphoma

C.

Aggressive

D.

Follicular lymphoma

E.

Stage IIIB

F.

Stage IIA

G.

Pruritis

H.

Non-Hodgkin lymphoma

I.

Very aggressive

J.

Diffuse large B cell lymphoma

K.

Indolent

L.

Burkitt’s lymphoma

M.

Epstein-Barr virus

N.

Pel-Ebstein fever

A

Burkitt’s lymphoma

878
Q

A classical but rare constitutional symptom of Hodgkin lymphoma

A.

Night sweats

B.

Hodgkin lymphoma

C.

Aggressive

D.

Follicular lymphoma

E.

Stage IIIB

F.

Stage IIA

G.

Pruritis

H.

Non-Hodgkin lymphoma

I.

Very aggressive

J.

Diffuse large B cell lymphoma

K.

Indolent

L.

Burkitt’s lymphoma

M.

Epstein-Barr virus

N.

Pel-Ebstein fever

A

A Pel Ebstein fever is one which has periods of high temperature separated by 15 to 28 day periods of normal temperature. Classically associated with Hodgekins lymphoma. Other differentials include tuberculosis and renal adenocarcinoma. Some physicians believe Pel-Ebstein fever doesn’t actually exist! For more information, see attached file.

879
Q

A 61 year old lady complains to her GP of morning stiffness and aching in her hips. She also suffers from anorexia, fatigue and occasional night sweats. She is found to have a raised ESR. Of note she has had giant cell arterititis in the past. What is the most likely diagnosis from the list above.

A.

Eosinophils

B.

Anaemia of chronic disease

C.

Microangiopathic haemolytic anaemia

D.

Monocytes

E.

Systemic lupus erythematosis

F.

Rheumatoid arthritis

G.

Polymyalgia rheumatica

H.

Iron deficiency anaemia

I.

Leucoerythroblastic anaemia

J.

Diverticular disease

K.

Neutrophils

A

Polymyalgia rheumatica

880
Q

An 81 year old man with known prostatic carcinoma presents to his GP with severe bone pain. Blood tests reveal a mild anaemia and peripheral blood film shows nucleated red blood cells and immature myeloid cells. What are these haematological features collectively known as?

A.

Eosinophils

B.

Anaemia of chronic disease

C.

Microangiopathic haemolytic anaemia

D.

Monocytes

E.

Systemic lupus erythematosis

F.

Rheumatoid arthritis

G.

Polymyalgia rheumatica

H.

Iron deficiency anaemia

I.

Leucoerythroblastic anaemia

J.

Diverticular disease

K.

Neutrophils

A

Leucoerythroblastic anaemia

881
Q

A 51 year old man is having work up for palliative surgery due to gastric adenocarcinoma. He is found to be anaemic, with high a reticulocyte count and fragmented red blood cells on blood smear. What is this anaemia known as?

A.

Eosinophils

B.

Anaemia of chronic disease

C.

Microangiopathic haemolytic anaemia

D.

Monocytes

E.

Systemic lupus erythematosis

F.

Rheumatoid arthritis

G.

Polymyalgia rheumatica

H.

Iron deficiency anaemia

I.

Leucoerythroblastic anaemia

J.

Diverticular disease

K.

Neutrophils

A

Microangiopathic haemolytic anaemia

882
Q

A 21 year old student recently returning from India complains to his GP of cough, headache and diarrhoea. He is febrile and rose spots are present on his chest. Blood culture reveals salmonella typhi. Which immune cells out of the list are most likely to be raised?

A.

Eosinophils

B.

Anaemia of chronic disease

C.

Microangiopathic haemolytic anaemia

D.

Monocytes

E.

Systemic lupus erythematosis

F.

Rheumatoid arthritis

G.

Polymyalgia rheumatica

H.

Iron deficiency anaemia

I.

Leucoerythroblastic anaemia

J.

Diverticular disease

K.

Neutrophils

A

Monocytes

883
Q

A markedly raised haemoglobin in a patient with renal cell carcinoma.

A.

Microangiopathic haemolytic anaemia

B.

Leucoerythroblastic anaemia

C.

Type 1 hypersensitivity reaction

D.

Secondary true polycythaemia

E.

Autoimmune haemolytic anaemia

F.

Rheumatoid arthritis

G.

Polycythaemia vera

H.

Parasitic infestation

I.

Brucella infection

J.

Acute fungal infection

A

Secondary true polycythaemia

884
Q

Monocytosis but with a normal neutrophil count.

A.

Microangiopathic haemolytic anaemia

B.

Leucoerythroblastic anaemia

C.

Type 1 hypersensitivity reaction

D.

Secondary true polycythaemia

E.

Autoimmune haemolytic anaemia

F.

Rheumatoid arthritis

G.

Polycythaemia vera

H.

Parasitic infestation

I.

Brucella infection

J.

Acute fungal infection

A

Brucella infection

885
Q

A markedly raised haemoglobin in a patient with splenomegaly

A.

Microangiopathic haemolytic anaemia

B.

Leucoerythroblastic anaemia

C.

Type 1 hypersensitivity reaction

D.

Secondary true polycythaemia

E.

Autoimmune haemolytic anaemia

F.

Rheumatoid arthritis

G.

Polycythaemia vera

H.

Parasitic infestation

I.

Brucella infection

J.

Acute fungal infection

A

Polycythaemia vera

886
Q

Neutrophilia with visible toxic granulation and vacuoles on the blood film. The monocyte count is normal.

A.

Microangiopathic haemolytic anaemia

B.

Leucoerythroblastic anaemia

C.

Type 1 hypersensitivity reaction

D.

Secondary true polycythaemia

E.

Autoimmune haemolytic anaemia

F.

Rheumatoid arthritis

G.

Polycythaemia vera

H.

Parasitic infestation

I.

Brucella infection

J.

Acute fungal infection

A

Acute fungal infection

887
Q

Sezary syndrome

A

Sézary syndrome is an aggressive form of a type of blood cancer called cutaneous T-cell lymphoma. Cutaneous T-cell lymphomas occur when certain white blood cells, called T cells, become cancerous; these cancers characteristically affect the skin, causing different types of skin lesions

888
Q

Prolonged APTT

Normal PT

Normal bleeding time

normal vWF

A

Haemophilia

889
Q

Prolonged APTT

Prolonged bleedeing time

Low vWF (normal in VWD2- functional abnormality)

Factor VIII levels may also be low

A

vWD

890
Q

A young boy is referred to you because of prolonged bleeding following circumcision. You also note some bleeding of the gums. Coagulation tests reveal a normal PT but a raised APTT and an increased Bleeding Time. Analysis of clotting factors reveals a low Factor VIII.

A

vWD

891
Q

A 9 month old boy presents to A&E with excessive bleeding following circumcision. Laboratory investigations reveal a prolonged activated partial thromblastin time (APTT), normal prothrombin time (PT) and a factor VIII level which is 10% of normal. Bleeding time is normal. What is the likely diagnosis?

A

Haemophilia A

892
Q

A 65-year-old man is referred to the haematology department by his GP after
initially presenting with tiredness, palpitations, petechiae and recent pneumonia.
His blood tests reveal Hb 9.8 (13–18 g/dL), MCV 128 (76–96 fL), reticulocyte
count 18 (25–100 × 109/L), 1.2 (2–7.5 × 109/L) and platelet count 125
(150–400 × 109/L).

B β-Thalassaemia
C Anaemia of chronic disease
D Blood loss
E Alcohol
F Vitamin B12 deficiency
G Renal failure
H Aplastic anaemia
I Lead poisoning

A

Aplastic anaemia (H) is caused by failure of the bone marrow resulting
in a pancytopenia and hypocellular bone marrow. Eighty per cent
of cases are idiopathic, although 10 per cent are primary (dyskeratosis
congenita and Fanconi anaemia) and 10 per cent are secondary (viruses,
SLE, drugs and radiation). The pathological process involves CD8+/
HLA-DR+ T cell destruction of bone marrow resulting in fatty changes.
Investigations will reveal reduced Hb, reticulocytes, neutrophils, platelets
and bone marrow cellularity as well as a raised MCV. Macrocytosis
results from the release of fetal haemoglobin in an attempt to compensate
for reduced red cell production.

893
Q

Microcytic hypochromic anaemia

Rouleaux formation

Raised ferritin

Reduced serum Fe and TIBC

A

ACD

894
Q

Normocytic anaemia

A

Blood loss can cause this due to the reduced number of circulating RBCs

895
Q

Basphillic stippling

Microcytic anaemia

A

Suggestive of Pb poisoning

896
Q

Causes of warm type AIHA

A

IgG mediated and occurs at 37 deg

Lymphoproliferative diseases

Autoimmune diseases

897
Q

Causes of cold type AIHA

A

IgM mediated and occurs at less than 4

Mycoplasma or EBV infection

898
Q

Rare stem cell disorder resulting in intravascular haemolysis, Hburia and thrombophilia

A

PNH

899
Q

Causes of anisocytosis

A

IDA most common

Thalassaemia

Megaloblastic anaemia

Sideroblastic anaemia all causative too

900
Q

Dacrocytes

A

Tear drop cells caused by myelofibrosis

901
Q

Blood film will demonstrate leuko-erythroblasts,
tear-drop cells and circulating megakaryocytes.

A

Myelofibrosis

Occurs due to extra-medullary haematopoeisis

Remember dry tap on BM aspirate with splenomegaly

902
Q

Causes of Heinz bodies

A

Most commonly caused by erythrocyte enzyme deficiencies i.e.

G6PDD

NADPHD

Chronic liver disease and alpha thalassaemia

903
Q

Rouleaux formation

A

Occurs in high plasma protein states e.g. MM

904
Q

Target cells

A

Erythrocytes with a central area of staining, ring of pallor and an outer ring of staining.

Formed in thalassaemia, asplenia and liver disease

905
Q

Pappenheimer bodies

A

Granules of iron found within erythrocytes

Pb poisoning

Sideroblastic anaemia

Haemolytic anaemia

906
Q

A Immune thrombocytopenic
purpura
B Idiopathic thrombotic
thrombocytopenic purpura
C Disseminated intravascular
coagulation
D Glanzmann’s thrombasthenia
E Von Willebrand disease
F Haemophilia A
G Haemophilia B
H Hereditary haemorrhagic
telangiectasia
I Bernard–Soulier syndrome

A 4-year-old girl is seen by her GP due to recent onset petechiae on her feet
and bleeding of her gums when she brushes her teeth. The child’s platelet count
is found to be 12 500 per μL. The GP prescribes prednisolone and reassures the
child’s mother that the bleeding will resolve.

A

Immune thrombocytopenic purpura (ITP; A) may follow either an acute or
chronic disease process. Acute ITP most commonly occurs in children, usually
occurring 2 weeks after a viral illness. It is a type 2 hypersensitivity
reaction, with IgG binding to virus-coated platelets. The fall in platelets is
very low (less than 20 × 109/L) but is a self-limiting condition (few weeks).
Chronic ITP is gradual in onset with no history of previous viral infection.
It is also a type 2 hypersensitivity reaction with IgG targeting GLP-2b/3a.

907
Q

Pentad in TTP

A

MAHA

Renal failure

Thrombocytopenia

Fever

Neurological signs

908
Q

Pathophysiology of TTP

A

Mutation in ADAM-ST13 gene coding for a protease that cleaves vWD allows for the formation of vWF multimers enabling platelet thrombi to form, causing organ damage

TTP, as with other microangiopathic hemolytic anemias (MAHAs), is caused by spontaneous aggregation of platelets and activation of coagulation in the small blood vessels. Platelets are consumed in the aggregation process, and bind vWF. These platelet-vWF complexes form small blood clots which circulate in the blood vessels and cause shearing of red blood cells, resulting in their rupture.[3]

Roughly, the two forms of TTP are idiopathic and secondary TTP. A special case is the inherited deficiency of ADAMTS13, known as the Upshaw-Schülman syndrome

909
Q

Investigations will reveal a high/
normal APTT, low factor 8 levels, low ristocetin cofactor activity, poor
ristocetin aggregation and normal PTT,

A

vWD

910
Q

A Factor V Leiden
B Antiphospholipid syndrome
C Malignancy
D Protein S deficiency
E Antithrombin deficiency
F Prothrombin G20210A mutation
G Oral contraceptive pill
H Buerger’s disease
I Chronic liver disease

1 A 35-year-old Caucasian man presents to accident and emergency with deep
pain and swelling in his left calf. His past medical history reveals history of
recurrent DVTs. The patient’s notes reveal a letter from his haematologist who
had diagnosed a condition caused by a substitution mutation.

A

Prothrombin G20210A (F) is an inherited thrombophilia caused by the
substitution of guanine with adenine at the 20210 position of the prothrombin
gene. Physiologically, prothrombin promotes clotting after
a blood vessel has been damaged. The G20210A causes the amplification
of prothrombin production thereby increasing the risk of clotting,
and causing a predisposition to deep vein thrombosis and pulmonary

embolism.
The prevalence of the mutation is approximately 5 per cent
in the Caucasian population, the race with the greatest preponderance.

911
Q

5 A 37-year-old man presents to accident and emergency with shortness of
breath and severe pleuritic chest pain. A CTPA reveals the diagnosis of pulmonary
embolism. The patient’s haematological records state the patient has a
condition that leads to the persistence of factors 5a and 8a causing increased
risk of venous thrombosis.

A

Protein S deficiency (D) is associated with the impaired degradation of
factors Va and VIIIa. Protein S and protein C are physiological anticoagulants.
Deficiency of protein S leads to persistence of factors 5a and
8a in the circulation and hence patients have a susceptibility to venous
thrombosis. Three types of protein S deficiency exist: type I (quantitative
defect) and types II and III (qualitative defect). Since protein S is a
vitamin K dependent anticoagulant, warfarin treatment and liver disease
may also lead to venous thrombosis in rare cases (the majority of cases
show increased bleeding).

912
Q

Why does pancreatic cancer predispose to thrombosis

A

Because tumour cells express tissue factor

913
Q

4 A 56-year-old man is given a blood transfusion following severe blood loss
after a hip replacement operation. Three hours after the transfusion, the patient
develops shortness of breath, a dry cough and a fever of 39°C.

A Immediate haemolytic transfusion
reaction
B Febrile non-haemolytic reaction
C Iron overload
D IgA deficiency
E Transfusion related lung injury
F Bacterial infection
G Delayed haemolytic transfusion
reaction
H Fluid overload
I Graft versus host disease

A

Transfusion-related lung injury (TRALI; E) is characterized by acute
non-cardiogenic pulmonary oedema that occurs within 6 hours following
blood transfusion. The pathogenesis of TRALI involves the presence
of anti-white blood cell antibodies in the donor blood that attack host
leukocytes; sensitizing events in donors include previous blood transfusion
or transplantation. Clinical features of TRALI are dry cough, dyspnoea
and fever.

914
Q

Which ABO incompatibility causes the most severe IHTR

A

Group O patient infused with group A blood

915
Q

What is delayed TR also known as

A

Non-ABo reacition

916
Q

A Acute lymphoblastic leukaemia
B Acute promyelocytic leukaemia
C Chronic myeloid leukaemia
D Chronic lymphocytic leukaemia
E Hairy cell leukaemia
F T-cell prolymphocytic leukaemia
G Large granular lymphocytic
leukaemia
H Adult T-cell leukaemia
I Acute myeloid leukaemia

2 A 41-year-old man is referred to a haematologist by his general practitioner
after several recent chest infections and tiredness. On examination, bruises
are seen on his lower limbs as well as splenomegaly. Initial blood tests reveal a
pancytopenia. Further testing demonstrates the presence of tumour cells that
express tartrate-resistant acid phosphatase

A

Hairy cell leukaemia (HCL; E) is a haematological malignancy of
B lymphocytes and a subtype of chronic lymphocytic leukaemia. It
most commonly occurs in middle-aged men. The cancer derives its
name from the fine hair-like projections that are seen on tumour cells
on microscopy. Cell surface markers include CD25 (IL-2 receptor) and
CD11c (adhesion molecule). Diagnosis can be confirmed by the presence
of tartrate-resistant acid phosphatase (TRAP) on cytochemical analysis.
Clinical features relate to invasion of the spleen (splenomegaly), liver
(hepatomegaly) and bone marrow (pancytopenia).

917
Q

Characteristic clover leaf appearance of nuclei

A

Adult T cell leukaemia

918
Q

caused by a translocation mutation forming
PML-RAR leading to proliferation of promyelocytes.

A

Acute promyelocytic leukaemia (APML; B) is the M3 subtype of acute
myeloid leukaemia

919
Q

The most common causative mutation is an inversion in chromosome
14: inv 14(q11;q32).

A

T-cell prolymphocytic leukaemia (T-PLL; F) is an aggressive T-cell leukaemia

920
Q

characterized by the presence
of large lymphocytes in the blood stream and bone marrow that
contain azurophilic granules.

A

Large granular lymphocytic leukaemia

921
Q

binucleate/multinucleate cells with abundant
cytoplasm, inclusion-like nucleoli and surrounded by eosinophils

A

Reed–Sternberg cells

922
Q

A 60-year-old man presents to his GP with malaise, night sweats and weight
loss. On examination the patient is found to have generalized lymphadenopathy
and hepatomegaly. Cytogenetic investigation a few weeks later by a haematologist
reveals a translocation between chromosomes 11 and 14, which has caused
overexpression of the BCL-2 protein

A Diffuse large B-cell lymphoma
B Burkitt lymphoma
C Follicular lymphoma
D Small lymphocytic leukaemia
E Mantle cell lymphoma
F Peripheral T-cell lymphoma
G Mycosis fungoides
H Angiocentric lymphoma
I Hodgkin’s lymphoma

A

Mantle cell lymphoma (MCL; E) is an aggressive B-cell lymphoma primarily
affecting elderly men. The most common cause is a translocation
between chromosomes 11 and 14, involving the BCL-1 locus and
Ig heavy chain locus, therefore leading to over-expression of cyclin D1.
Over-expression of cyclin D1 leads to dysregulation of the cell cycle.
Clinically, generalized lymphadenopathy, as well as bone marrow and
liver infiltration, are common. Hodgkin’s lymphoma can be split into
classical and lymphocyte predominant nodular (LPN) subtypes.

923
Q

A Diffuse large B-cell lymphoma
B Burkitt lymphoma
C Follicular lymphoma
D Small lymphocytic leukaemia
E Mantle cell lymphoma
F Peripheral T-cell lymphoma
G Mycosis fungoides
H Angiocentric lymphoma
I Hodgkin’s lymphoma

A 40-year-old woman is referred to a haematologist after she is found to have
generalized, painless lymphadenopathy. A report on tumour cell morphology
states the presence of both centrocytes and centroblasts.

A

Follicular lymphoma (C) is caused most commonly by a translocation
between chromosomes 14 and 18, leading to over-expression of the
BCL-2 protein. Over-expression of BCL-2 causes inhibition of apoptosis,
promoting the survival of tumour cells. Tumour cells in follicular
lymphoma are characterized by centrocytes (small B cells with irregular
nuclei and reduced cytoplasm) and centroblasts (larger B cells with
multiple nuclei). Clinical features include painless, generalized lymphadenopathy.
Follicular lymphoma usually presents in middle-aged patients
and has a non-aggressive course but is difficult to cure.

924
Q

A Diffuse large B-cell lymphoma
B Burkitt lymphoma
C Follicular lymphoma
D Small lymphocytic leukaemia
E Mantle cell lymphoma
F Peripheral T-cell lymphoma
G Mycosis fungoides
H Angiocentric lymphoma
I Hodgkin’s lymphoma

62-year-old HIV-positive man presents to a haematologist with a 3-month
history of weight loss and tiredness. On examination, the patient has a mass on
his neck which the patient states has been rapidly growing. Staining of biopsy
tissue demonstrates the present of large B cells which are positive for EBV.

A

Diffuse large B-cell lymphoma (DLBL; A) is a haematological malignancy
most commonly affecting the elderly, characterized by large lymphocytes
which have a diffuse pattern of growth. Common chromosomal abnormalities
which contribute to the development of DLBL include the t(14;18)
translocation which is characteristic of follicular lymphoma; this suggests
that follicular lymphoma may undergo a degree of transformation to cause
DLBL in such circumstances. Tumour cells that have follicular lymphoma
morphology may be present at other sites. Two subtypes of DLBL have been
described, both of which are associated with immunodeficiency: immunodeficiency-
associated large B-cell lymphoma (linked to latent EBV infection)
and body cavity-based large cell lymphoma (linked to HHV8 infection).

925
Q

indistinguishable from chronic
lymphocytic leukaemia (CLL) in terms of genetics and morphology but
more commonly presents with greater peripheral blood lymphocytosis
than CLL.

A

Small lymphocytic lymphoma

926
Q

presents in adulthood as cutaneous masses
most commonly in the nasal area. Tumour cells will express NK-cell
markers and commonly may be infected with EBV.

A

Angiocentric lymphoma

927
Q

A 72-year-old man presents with a 1-month history of fever, night sweats and
weight loss. Blood tests reveal a monocyte count of 1400/mm3 in the peripheral
blood and a bone marrow biopsy demonstrates that myeloblasts constitute 16
per cent of his bone marrow.

A Essential thrombocythaemia
B Myelofibrosis
C Chronic myelo-monocytic
leukaemia
D Refractory anaemia with excess
blasts
E Polycythaemia rubravera
F Refractory anaemia with ringed
sideroblasts
G Refractory anaemia
H 5q-Syndrome
I Multiple myeloma

A

Chronic myelo-monocytic leukaemia (CMML; C) is a myelodysplastic/
myeloproliferative disease which most commonly affects the elderly
population, defined by a monocytosis of >1000/mm3 and increased
number of monocytes in the bone marrow. Myeloblasts make up <5
per cent of the peripheral blood and <20 per cent of the bone marrow.
Eosinophilia may be present in CMML associated with a t(5;12) translocation.
The Philadelphia chromosome BCR/ABL fusion gene is not
responsible for causing CMML. Commonly, patients will present with
fever, fatigue, night sweats; on examination hepatomegaly and/or more
commonly splenomegaly may be present.

928
Q

Features include hypo-lobulated megakaryocytes and an increased/
normal platelet count.

A

5q-Syndrome (H) is caused by deletion of the long arm of chromosome
5.

929
Q

is defined by fewer than 5 per cent myeloblasts
present in the bone marrow.

A

Refractory anaemia

930
Q

is a myelodysplastic
disease characterized by fewer than 5 per cent myeloblasts in the bone
marrow, but greater than 15 per cent erythrocyte precursors stuffed with
iron in their mitochondria.

A

Refractory anaemia with ringed sideroblasts

931
Q

Refractory anaemia with excess blasts (D)

A

is a myelodysplastic disease
that may be classified into type 1 (5–9 per cent myeloblasts in the bone
marrow) or type 2 (10–19 per cent myeloblasts in the bone marrow).

932
Q

Pathophysiology in ACD

A

Il-6 produced by macrophages induced hepcidin production by the liver which has the effect of retaining Fe in macrophages and decreases export from enterocytes (thus reducing plasma iron levels)

933
Q

What conditions can cause a monocytosis

A

Sarcoidosis

Brucellosis, typohid, VZV

CMML

934
Q

Features of FHTR

A

Febrile haemolytic transfusion reactions (A) typically occur less than
24 hours after the transfusion. These reactions are thought to be due to
antibodies in the patient reacting with white cell antigens in the donor
blood, or due to cytokines which build up in the blood products during
storage. These reactions usually only warrant slowing the transfusion,
and giving an anti-pyretic if needed.

935
Q

Pencil cells

A

Type of elliptocyte that occur in IDA, thalassaemia and PK deficiency

936
Q

Howell-Jolly bodies

Target cells

Occasional nucleated RBCs

Lymphocytosis

Macrocytosis

Acanthocytes

A

Hyposeplnism

937
Q

Target cells

the 3 Hs

A

Hepatic pathology

Hyposplenism

Hbopathies

938
Q

spiculated red cells that are found in hyposplenism,
α-β-lipoproteinaemia, chronic liver disease and α-thalassaemia trait

A

Acanthocytes

939
Q

The PIIES

A

Haematological diseases in which splenectomy may be of benefit

Thalassaemias

Pyrukvate kinase

Immune haemolytic anaemia

Idiopathic thyrombocytopenic purpura

Elliptocytosis

Spherocytosis (hereditary)

940
Q

HbA

A

a2

b2

941
Q

HbA2

A

a2

d2

942
Q

HbF

A

a2

g2

943
Q

HbC

A

these patients may have a mild splenomegaly and haemolytic
anaemia. Haemoglobin C is similar to haemoglobin S in that it comprises
two normal alpha chains and two variant beta chains in which lysine
has replaced glutamic acid at position 6.

944
Q

Pathogenesis of aplastic crises in parvovirus infection and SCD

A

The virus affects erythropoiesis by invading erythrocyte precursors and
destroying them. Infants and children with sickle cell disease initially
have no immunity to parvovirus B19, and their first exposure can lead
to pure red cell aplasia. In a normal individual the virus blocks red
cell production for 2 or 3 days with little consequence, but it can be
life threatening in sickle cell patients in whom the red cell life span is
already shortened. This can lead to profound anaemia over the course
of just a few days, and a dramatic drop in the reticulocyte count. Serum
IgM antibodies to parvovirus B19 can confirm the diagnosis, and blood
transfusion may be required.

945
Q

A 26-year-old pregnant woman is found to have an Hb of 9.5 g/dL on a routine
blood test, with an MCV of 70. Serum electrophoresis reveals an Hb A2 of
3.9 per cent and Hb A of 96.1 per cent. Her ferritin levels are normal. The most
likely diagnosis is:
A Iron deficiency anaemia
B Cooley’s anaemia
C b-Thalassaemia intermedia
D b-Thalassaemia minor
E a-Thalassaemia

A

b-Thalassaemias are a group of genetic haemoglobinopathies that
essentially
result in reduced or absent formation of the beta chains of
haemoglobin leading to anaemia of varying degrees of severity. They are
prevalent in the Middle East, Central, South and South East Asia, Southern
China and around the Mediterranean. There are three main forms:
thalassaemia major, thalassaemia intermedia and thalassaemia minor.

In b-thalassaemia minor (D) only one of the b-globulin alleles is mutated,
so these individuals usually only have a well-tolerated microcytic anaemia
(Hb >9 g/dL) which is clinically asymptomatic. They might be picked
up on a routine blood test, with a low MCH and significantly low MCV
(<80 fL). They also have an increase in the fraction of Hb A2, as in this
case. In most people the fraction of Hb A2 (α2δ2) will be 1.5–3.5 per
cent, but in b-thalassaemia minor the proportion of Hb A2 is >3.5–4 per
cent to compensate for the reduced amount of normal haemoglobin, and
they might have a slight increase in Hb F. It can worsen in pregnancy, as
in this case

946
Q

Cooley’s anaemia=

A

Beta thalassaemia major

947
Q

Cold LID

A

Cold AIHA

Lymphoproliferative disease e.g. CLL, lymphomas

Infections: mycoplasma, EVC

Don’t know i.e. idiopathic

948
Q

Treatment of cold AIHA

A

Avoiding cold conditions

Chlorambucil

Treat underlying cause

949
Q

Treatment of warm AIHA

A

Steroids

Ig

Splenectomy

950
Q

Presentation of PNH

A

Pancytopenia

New thrombus

HA

Paroxysmal nocturnal haemoglobinuria (B) is another rare acquired disease,
but one that is potentially life threatening. The resulting defect in
the red cell membrane leads to intravascular haemolysis. The disease has
three aspects: the most common way for it to present is with a haemolytic
anaemia, which may cause haemoglobinuria, especially overnight.
The second aspect is thrombophilia, which can present with visceral
thrombosis (e.g. CNS, pulmonary, mesenteric). The third aspect is deficient
haematopoiesis which can cause a pancytopenia with aplastic anaemia.

951
Q

A 34-year-old woman with known Addison’s disease is brought to the GP by her
husband, as he is concerned that she keeps falling over at night. On examination
the GP notes that she has conjunctival pallor. A thorough neurological examination
reveals absent knee jerks, absent ankle jerks and extensor plantars bilaterally. Which
of the following is the most sensitive test for the condition she has developed?
A Anti-intrinsic factor antibodies
B Anti-endomysial cell antibodies
C Anti-smooth muscle antibodies
D Anti-parietal cell antibodies
E Anti-voltage gated calcium channel antibodies

A

Intrinsic factor antibodies (A) can be found in approximately 50 per
cent of patients, and are specific for pernicious anaemia but not as
sensitive as anti-parietal cell antibodies (D) which are found in >90
per cent of patients.

This woman has developed pernicious anaemia leading to vitamin B12
deficiency. It can be associated with other autoimmune conditions, such
as Addison’s disease or thyroid disease. Specifically, she has developed
a condition called subacute combined degeneration of the cord (SACD)
which has led to symmetrical loss of dorsal columns (resulting in loss
of touch and proprioception leading to ataxia, and LMN signs) and corticospinal
tract loss (leading to UMN signs), with sparing of pain and
temperature sensation (which is carried by spinothalamic tracts). The
ataxia and loss of joint position sense have resulted in her falling at
night, which may be exacerbated by optic atrophy – another manifestation
of vitamin B12 deficiency.
Remember that vitamin B12 is found in meat, fish and dairy products.
More common causes of vitamin B12 deficiency can be related to diet
(e.g. vegans) or to malabsorption. It is absorbed in the terminal ileum
after binding to intrinsic factor produced by the parietal cells in the
stomach. Causes of malabsorption can therefore be related to the stomach
(e.g. post gastrectomy, pernicious anaemia), or due to the terminal ileum
(e.g. Crohn’s, resection of the terminal ileum, bacterial overgrowth).
Pernicious anaemia is caused by an autoimmune atrophic gastritis when
autoantibodies are produced against parietal cells and intrinsic factor

itself. The lack of B12 impairs DNA synthesis in red blood cells, leading
to the production of large, megaloblastic erythrocytes.

952
Q
  • Low haemoglobin
  • High MCV
  • Low platelets and WCC if severe
  • Hypersegmented neutrophils
  • Megaloblasts in the bone marrow
  • Cabot rings in RBCs
A

B12 deficiency

953
Q

Causes of macrocytosis

A
  1. Megaloblastic: folate and B12 deef
  2. Non-megaloblastic RALPH
  3. Other haematological disorders e.g. myelodysplasia, aplastic anaemia, myeloma, myeloproliferative disorders
954
Q

RALPH

A

Non-megaloblastic causes of macrocytic anaemia

Reticulocytosis

Alcohol

Liver disease

Pregnancy

Hypothyroidism

955
Q

Drugs causing aplastic anaemia

A

All the Cs

Cytotoxics

Carbamezepine

Chloramphenicol

Anticonvulsants- phenytoin

956
Q

A 50-year-old diabetic man sees his GP complaining of generalized tiredness and
a painful right knee. He is found on examination to have five finger breadths of
hepatomegaly. An X-ray of his right knee is reported as showing chondrocalcinosis.
His blood tests are likely to reveal:
A Raised MCV
B Raised total iron binding capacity
C Reduced serum ferritin
D Reduced iron level
E Raised transferrin saturation

A

This man has hereditary haemachromatosis, an inherited disorder of
iron metabolism. It is particularly common in those of Celtic descent,
and the gene responsible for the majority of cases is the HFE gene on
chromosome 6.
Increased iron absorption leads to deposition to multiple organs including:
• the liver (hepatomegaly, deranged LFTs)
• joints (arthralgia, chondrocalcinosis)
• pancreas (diabetes)
• heart (dilated cardiomyopathy)
• pituitary gland (hypogonadism and impotence)
• adrenals (adrenal insufficiency)
• skin (slate grey skin pigmentation)
Blood tests can show deranged LFTs as in this case, as well as a raised
serum ferritin, raised serum iron, reduced or normal total iron binding
capacity and raised transferrin saturation (E) (>80 per cent).

957
Q

Low Fe

High TIBC/transferrin

Low transferrin saturation

Low ferritin

A

IDA

958
Q

High Fe

Low or normal TIBC/transferrin

Low Transferrin saturation

High ferritin

A

Haemochormatosis

959
Q

Low Fe

Low TIBC/Transferrin

Low transferrin saturation

High ferritin

A

ACD

960
Q

High iron

Low TIBC/transferrin

High transferrin saturation

High ferritin

A

Chronic haemolysis

961
Q

A 67-year-old woman presented with polyuria and polydipsia on a background
of ongoing bone pain. Her blood tests revealed a high calcium, and a serum
electrophoresis was sent. Her serum paraprotein was 25 g/L and a bone marrow
biopsy revealed 6 per cent clonal plasma cells. The most likely diagnosis is:

A Plasma cell dyscrasia
B Monoclonal gammopathy of undetermined significance
C Smouldering myeloma
D Multiple myeloma
E Hypercalcaemia with no evidence of underlying malignancy

A

Symptomatic myeloma (D):

962
Q

Clonal plasma cells on bone marrow biopsy
• Paraprotein in either serum or urine
• Evidence of end-organ damage attributed to the plasma cell
disorder, commonly remembered using the acronym ‘CRAB’
(Calcium – high, Renal insufficiency, Anaemia and Bone lesions)

A

Symptomatic myeloma (D):

963
Q
  • Serum paraprotein >30 g/L AND/OR
  • Clonal plasma cells >10 per cent on bone marrow biopsy AND
  • NO myeloma-related organ or tissue impairment
A

Asymptomatic (smouldering) myeloma (C):

964
Q
  • Serum paraprotein <30 g/L AND
  • Clonal plasma cells <10 per cent on bone marrow biopsy AND
  • NO myeloma-related organ or tissue impairment
A

Monoclonal gammopathy of undetermined significance (MGUS)

965
Q

A 39-year-old motorcyclist is admitted following a road traffic accident complicated
by severe burns. Several days later he is due to go home, when oozing
is noted from his cannula site and he has several nose bleeds. Repeat blood
tests reveal an Hb of 12.2 g/dL, WCC of 11.2 × 109/L, and platelets of 28 × 109/L.
A coagulation screen shows a prolonged APTT and PT. He also has a reduced
fibrinogen and raised D-dimers. The most likely diagnosis is:
A Liver failure
B Disseminated intravascular coagulation
C Thrombotic thrombocytopenic purpura
D Aplastic anaemia
E Heparin induced thrombocytopenia

A

This man has developed disseminated intravascular coagulation (DIC)
(B) following his severe burns. DIC is widespread pathological activation
of the clotting cascade in response to various insults. The cascade
is activated in various ways: one mechanism is the release of a transmembrane
glycoprotein called ‘tissue factor’ in response to cytokines or
vascular damage. This results in fibrin formation, which can eventually
cause occlusion of small and medium sized vessels and lead to organ
failure. At the same time, depletion of platelets and coagulation proteins
can result in bleeding (as in this case).

966
Q

Causes of DIC
I’M STONeD

A

Immunological e.g. severe allergic reactions

Miscellaneous e.g. aortic aneurysm, liver disease

Sepsis

Trauma

Obstetric e.g. amniotic fluid embolism, placental abruption

Neoplastic

Drugs and toxins

967
Q

Blood tests will typically reveal a thrombocytopenia,
raised PT and APTT, decreased fibrinogen and increased
D dimers.

A

DIC

968
Q

MARCH with low plt

A

TTP

MAHA

A fever

Renal failure

Fluctuating CNS signs

Haematuria/proteinuria

Low platelet count

969
Q

caused by the spirochaete Leptospira interrogans, and is spread by
infected rat urine. Although it can cause an abrupt onset of renal failure
and a fever, it would not typically result in thrombocytopenia or features
of MAHA.

A

Weil’s disease

970
Q
A
971
Q
A
972
Q
A
973
Q
A
974
Q
A
975
Q
A
976
Q
A
977
Q

A 56-year-old woman with known cirrhosis presents with falls. On examination
she is clinically jaundiced and rectal examination reveals malaena. Blood tests
reveal an INR of 2.2. She is diagnosed with decompensated chronic liver disease.
Which of the following is not a vitamin K dependent clotting factor?
A Thrombin
B Factor VII
C Factor VIII
D Protein C
E Factor X

A

C

978
Q

What are the vitamin K dependant clotting factors?

A

II

VII

IX

X

Protein C S and Z

979
Q

How does Warfarin influence clotting facotr production

A

Still produced but they lack efficacy due to an inability to interact with calcium or platelet facotr 3

980
Q

What are the phases of the exrinsic pathway

A

Initiation phase:

Factor VIIa activates downstream factors Ix and X

Amplification phase:

Xa/Va activates prothrombin to thrombin which then activates XI, VIII and V resulting in the prothrombinase complex

This explodes with thrombin generating activity to produce fibrin rapidly and stabilise the platelet clot= propagation phase

981
Q

Patients with chronic abdominal pain, weight loss, raised ESR with
a known abdominal aneurysm should prompt the thought of

A

an inflammatory
aneurysm subtype.

In these patients the inflammatory process
sometimes encases the nearby ureters causing obstruction and eventually
hydronephrosis.

982
Q

A 62-year-old man presents with shortness of breath. This has been gradually
getting worse for the last few years and is associated with chronic productive
cough. He is a heavy smoker. His chest X-ray reveals a hyperexpanded chest
with no other abnormalities. His bloods tests are normal except for a raised haemoglobin
and raised haematocrit. What is the most likely cause for this?
A Polycythaemia rubra vera
B Idiopathic erythrocytosis
C Secondary polycythaemia
D Gaisbock’s disease
E Combined polycythaemia

A

Combined polycythaemia (E), also known as smoker’s polycythaemia,
has multiple aetiological factors. Cigarettes contain high concentrations
of carbon monoxide gas which bind avidly to haemoglobin, thus
displacing oxygen. This leads to increased erythropoietin (EPO) secretion
from the hypoxic renal interstitium. EPO promotes erythrocyteproliferation
and differentiation and prevents their apoptosis in the bone
marrow, thus increasing red cell mass. Smoking is also a significant risk
factor for chronic obstructive pulmonary disease, which is what this
man suffers from. The obstructed airways reduce oxygen delivery to
the alveoli and pulmonary vessels they supply thus causing a reduction
of oxygen supply furthering the hypoxia. Finally, smokers also have
an associated reduced plasma volume, thus increasing the relative concentration
of haemoglobin. This is therefore ‘combined’ because of the
presence of both increased red cell mass and reduced plasma volume.

983
Q

Gaisbock’s disease

A
Haemoglobin may be raised with relative deficiency
of plasma (i.e. relative or apparent polycythaemia, historically known
as Gaisbock’s disease (D)).
984
Q

the label given to those with polycythaemia secondary to JAK2 mutation,
but not with the V617F exon 14 mutation, e.g. exon 12 mutations.

A

Idiopathic erythrocytosis (B)

985
Q

What is important to note re a positive diptick for blood?

A

May represent Hburia or myoglobinuria

986
Q

an acquired clonal stem
cell disorder characterized by an abnormal erythrocyte sensitivity to
the lytic complement pathway. There is a deficiency of glucosyl phosphatidyl
inositol (GPI) linked proteins namely CD55 (decay-accelerating
factor) and CD59 (membrane inhibitor or reactive lysis).

A

Paroxysmal nocturnal haemoglobinuria

987
Q

Causes of MAHA

A

Mechanical destruction of RBCs

E.g. Heart valve

DIC

TTP

HUS

988
Q

What differentiates between apparent and true polycythaemia

A

Red cell count is measured as the number of
erythrocytes in a quantum of plasma, whereas red cell mass is determined
by isotope studies quoted as mL/kg. It is a measure of absolute
red cell mass and is therefore not affected if someone is dehydrated, for
example, where the relative plasma volume is reduced giving a falsely
high red cell concentration. There are many situations where the red cell
concentration and red cell mass do not parallel each other, e.g. vomiting,
diarrhoea or overuse of diuretics. If a patient has increased red cell
concentration this may therefore be absolute or relative – the latter
being secondary to reduced plasma volume thus making the polycythaemia
secondary to haemoconcentration. Absolute polycythaemia may
be primary or secondary.

989
Q

von Willebrand’s disease is characterized by abnormal platelet aggregation when
they are exposed to:
A Streptomycin
B Aspirin
C Fibrinogen
D Collagen
E Ristocetin

A
von Willebrand’s disease (vWD) is characterized by a quantitive or
qualititative defect in von Willebrand factor (vWF). Ristocetin, an antibiotic
no longer used clinically, causes vWF to bind the platelet receptor
glycoprotein Ib (GlpIb) through an unknown mechanism. If ristocetin
is added to platelets with defective vWF or defective GlpIb (called
Bernard–Soulier syndrome) then platelet aggregation does not occur. It
will occur, however, with other pro-aggregative factors including collagen
(D) and fibrinogen (C). If vWF or GlpIb is absent, aggregation does
not occur with collagen as there is no molecular link between collagen
and the platelet. However, this is the case with all patients with vWF.
990
Q

Inherited platelet defects

A

Glanzmann’s thrombasthenia (an inherited lack of GlpIIb/IIIa)
where fibrinogen cannot cross-link platelets during the initial platelet
aggregative stage of thrombosis. Understanding these receptors and
their importance in platelet aggregation has led to the development of
powerful antiplatelet medications including adciximab, eptifibatide and
tirofiban. Other inherited platelet diseases include storage pool diseases,
e.g. grey platelet syndrome, Quebec platelet disorder, Hermansky–Pudlak
syndrome and Chediak–Higashi syndrome. These refer to defects of the
alpha and dense granules in the platelet which are released to promote
platelet aggregation.

991
Q

What is the mechanism through which DS may increase the chance of AML

A

Dosage affect due to chromosome 21 duplication

992
Q

associated with translocation and
dysregulation of the c-myc gene on chromosome 8 including t(8;14),
t(2;8) and t(8;22).

A

Burkitt’s lymphoma

993
Q

Histologically, a nodular growth pattern with
a mixture of centrocytes and centroblasts is characteristic. The proportion
of centroblasts found determines the tumour grade which has therapeutic
implications. These cells are CD10 and BCL-6 positive in the majority. It
is usually indolent but can transform into a high grade lymphoma

A

Follicular lymphoma

994
Q

arises mainly at extranodal sites due to
chronic antigenic stimulation and malignant transformation. It is a
B-cell NHL arising from marginal cells in the lymph node. There are
clinically three subtypes: extranodal marginal zone B-cell lymphoma of
mucosa associated lymphoid tissue (MALT); nodal marginal zone B-cell
lymphoma; and splenic marginal zone B-cell lymphoma

A

Marginal zone lymphoma

995
Q

usually affects elderly men presenting with lymphadenopathy and constitutional
‘B’ symptoms (weight loss, fever, drenching night sweats) in
one-third. It is the most common histological subtype of NHL. The diagnosis
is usually made with an excisional biopsy demonstrating pan-B
cell markers, e.g. CD20, and CD79a. Histologically, there is effacement
of normal architecture by sheets of atypical lymphoid cells. The cell of
origin is the centrob

A

DLBL

996
Q

It typically affects middleaged
men with lymphadenopathy and gastrointestinal tract involvement
including spleen and Waldeyer’s ring. It usually presents with advanced
disease and involves any region of the GI tract occasionally presenting
as multiple intestinal polyps. Nuclear staining for cyclin D1 is present
in 95 per cent of cases and is strongly associated with the t(11;14)
(q13;q32) mutation – a translocation between cyclin D1 locus and
immunoglobulin heavy chain locus. This

A

Mantle cell lymphoma

997
Q

This cell is known as the lymphocytic and histiocytic cell
or L&H variant. Sometimes these cells are referred to as ‘popcorn’ cells
because their nucleus resembles an exploded popcorn kernel. This subtype
of HL accounts for 5 per cent of cases and has a bimodal age distribution
– children and adults between the ages of 30 and 40.

A

Nodular lymphocytic HL

(Non-classical)

998
Q

is characterized by at least a partially
nodular grown pattern, with fibrous bands separating nodules.

A

Nodular sclerosing classical HL

999
Q

heterogeneous group with a diffuse
or vaguely nodular growth patter without band-forming sclerosis.

A

Mixed cellularity HL

1000
Q

most commonly has a nodular growth pattern. In
this subtype, cells resembling L&H variants may be present making the
distinction from non-classical lymphoma more difficult. The background
infiltrate consists predominantly of lymphocytes, with rare eosinophils
or neutrophils.

A

Lymphocyte rich HL

1001
Q

subtype has a diffuse growth
pattern and appears hypocellular with a lack of inflammatory cells. This
subtype has a poor prognosis.

A

HL lymhpocyte depleted

1002
Q

Why can women be affected in G6PD?

A

Unlike some other X-linked conditions,
women can be affected due to the random nature of X chromosome
inactivation (lyonization) which leads to some cells being vulnerable
to oxidative stress.

1003
Q

Haptoglobin in intravascular and extravascular haemolysis

A

Haptoglobin circulates in the plasma and avidly binds to
free haemoglobin to be later removed by the reticuloendothelial system.
It is therefore reduced in intravascular haemolysis only. Extravascular
haemolysis occurs mainly in the spleen where free haemoglobin is not
released into the circulation and therefore haptoglobin levels are generally
unchanged.

1004
Q

A 35-year-old Asian woman presents with tiredness. The full blood count shows:
Haemoglobin: 10.1 g/dL (11.5–16.5)
Platelet count: 160 × 109 (150–400 × 109)
White cell count: 6.6 × 109 (4–11 × 109)
Mean cell volume: 62 fL (80–96 fL)
Hb A2: 6.3 per cent (2–3 per cent)
Which of the following is the most likely diagnosis?
A Sickle cell disease
B Acute myeloid leukaemia
C b-Thalassaemia major
D b-Thalassaemia trait
E Hereditary spherocytosis

A

This woman presents with microcytic anaemia, the most common cause
of which is iron deficiency. However, the mean cell volume is disproportionally
reduced compared with the degree of anaemia indicating there
might be a haemoglobinopathy present. The presence of increased Hb A2
confirms the diagnosis of b-thalassaemia trait.

1005
Q

raised RDW with increased MCHC is very suggestive of this condition.

A

Hereditary psherocytosis

1006
Q

A 62-year-old man presents with bruising and tiredness. Examination reveals
moderate splenomegly and his a reveal a normocytic anaemia with blood tests
platelet count of 900 × 109/L, neutrophilia, basophilia, numerous myelocytes and
4 per cent myeloblasts. The neutrophils have low leukocyte alkaline phosphatase
levels. Which of the following is likely to be present in this patient?
A t(9;22)
B t (8;14)
C BCR-Abl fusion gene only
D V617F point mutation in JAK2
E 5q-Syndrome

A

This patient exhibits features of chronic myeloid leukaemia as evidenced
by raised myeloid lineage cells including neutrophils, myelocytes
and basophils. The neutrophils are morphologically normal but
cytochemically different – a laboratory test sometimes used to differentiate
between reactive or leukaemoid neutrophilia and CML is the
leukocyte alkaline phosphatase. It is normal or high in the former, but
characteristically low in CML. Absolute basophilia is a universal finding
in CML, with absolute eosinophilia found in 90 per cent of cases.
A raised platelet count is also common in CML; a low platelet count,
however, should make one reconsider the diagnosis, e.g. myelodysplastic
syndromes

1007
Q

Which of the following patients has the worse prognosis?
A 25-year-old man with inguinal lymphadenopathy
B 25-year-old woman with mediastinal and inguinal lymphadenopathy
C 25-year-old woman with mediastinal and inguinal lymphadenopathy and
night sweats
D 25-year-old woman with mediastinal and inguinal lymphadenopathy with
5 per cent weight loss in last 6 months
E 25-year-old man with cervical and mediastinal lymphadenopathy

A

This question relies on the candidate’s knowledge and understanding of
the Ann Arbor staging system. This clinical staging system is relatively
intuitive – stages are between I and IV either in the absence or presence
of ‘B symptoms’. A simplified version of the classification is as follows:
• Stage I: involvement of a single lymph node region
• Stage II: involvement of two or more lymph node regions on the
same side of the diaphragm
• Stage III: involvement of lymph nodes on both sides of the
diaphragm
• Stage IV: extranodal spread (not spleen however, this is taken as a
lymph node)

The definition of B symptoms includes significant unexplained fever,
night sweats or unexplained weight loss of over 10 per cent during
6 months prior to diagnosis

Patient A would therefore be classified as Ia, patient B as
IIa, patient C as IIIb, patient D as IIIa, technically as she does not quite
fulfil the 10 per cent loss in 6 months and finally patient E as stage
IIa. Note that in Hodgkin’s lymphoma, the disease always spreads contiguously
whereas in non-Hodgkin’s lymphoma this is not always the
case.

1008
Q

A patient presents with acute promyelocytic leukaemia. What is the most likely
mechanism of underlying leukaemogenesis?
A Telomere shortening
B Aberrant fusion of two genes
C Impaired protein degredation
D Over-expression of cellular oncogene
E Post-translational modification

A

B Acute promyelocytic leukaemia is interesting for a number of reasons.
There is a reciprocal translocation between the long arms of chromosomes
15 and 17 giving the PML-RARA fusion gene (B).

This links the
retinoic acid receptor alpha (RARA) gene on chromosome 17 with the
promyelocytic leukaemia (PML) gene on chromosome 15. RARA is a
member of a family of retinoin-binding transcription factors that regulate
gene expression. It heterodimerizes with retinoid X receptor (RXR)
and binds to retinoic acid response elements to influence gene transcription.
In the absence of retinoic acid, the RARA/RXR dimer interacts
with another protein (nuclear corepressor) to repress gene transcription.
Therefore, addition of retinoic acid stimulates gene transcription. In
the setting of promyelocytic leukaemia, retinoic acid induces myeloid
differentiation
which is abnormally halted thus providing remission
by encouraging cell differentiation rather than cell death. The second
reason
this type of leukaemia is interesting is its association with disseminated
intravascular coagulopathy. The pathogenesis is not completely
understood but recognizing it early is important as treatment
with retinoic acid plus supportive therapy can lead to rapid improvement
in the coagulopathy.

1009
Q

A 16-year-old girl with mild von Willebrand’s disease is scheduled for a dental
extraction. She has had one previously where she required two units of blood
transfused. What is the most appropriate treatment for this patient prior to
surgery?
A Cryoprecipitate
B Desmopressin
C Fresh frozen plasma
D Vitamin K
E Recombinant factor VIII concentrate

A

This woman has mild von Willebrand’s disease (vWD) which can be
treated with desmopressin (B). There are three types of vWD – type I is
a quantitative deficiency of von Willebrand Factor (vWF), type II is a
qualitative defect in vWF whereas type III results in profound deficiency
in vWF. There are four subtypes of type II vWF (2A, 2B, 2M and 2N).
vWF is important in two ways; first it acts as a bridge between platelets
and between platelets and subendothelial structures at the site of
injury; and second it carries factor VIII which is a key molecule in the
clotting cascade. Desmopressin acts to increase vWF and factor VIII
concentration by encouraging its release from endothelial cell storage
sites. Desmopressin is efficacious in type I and most type II disease but

not in type III. This woman is known to have ‘mild’ disease thus making
desmopressin a viable option

Interestingly, desmopressin in patients
with type 2B will lead to a transient worsening of their thrombocytopenia.
Patients with type 2B vWD have increased binding of the abnormal
vWF to platelets causing sequestration and clearance of platelets.
This is worsened for desmopressin, if only for a few hours. Despite this,
there have been reports of patients benefiting from desmopressin.

1010
Q

An 80-year-old man presents with tiredness and lethargy. After initial work-up,
a diagnosis of myelodysplastic syndrome is suspected. Which of the following is
true about this condition?
A A blood film will typically show neutrophil toxic granulation
B If there are 1 per cent blasts of the total white cell count, this represents
leukaemic transformation
C Cytotoxic chemotherapy is first line treatment
D Mortality is more likely to be from infection than leukaemic transformation
E Absence of the short arm of chromosome 5 is a subtype

A

The myelodysplastic syndromes are a heterogeneous group of conditions
characterized by an abnormal clone of stem cells with impaired proliferation
and differentiation. The result is a peripheral cytopenia, qualitative
abnormalities in erythroid, myeloid and megakaryocyte maturation,
as well as increased risk of leukaemic transformation. The abnormalities,
both quantitative and qualitative, in neutrophils mean susceptibility to
bacterial infection is high and thus a corresponding increased likelihood
of mortality (D). Skin infections are particularly common and resistant
to treatment.

1011
Q

An 80-year-old man presents with tiredness and lethargy. After initial work-up,
a diagnosis of myelodysplastic syndrome is suspected. Which of the following is
true about this condition?
A A blood film will typically show neutrophil toxic granulation
B If there are 1 per cent blasts of the total white cell count, this represents
leukaemic transformation
C Cytotoxic chemotherapy is first line treatment
D Mortality is more likely to be from infection than leukaemic transformation
E Absence of the short arm of chromosome 5 is a subtype

A

Absence of the long arm of chromosome 5 is a specific subtype of MDS.
There is an interstitial deletion and it most commonly affects elderly
women. It may respond quite dramatically to lenolidamide, a thalidomide
derivative. Deletion of the short arm of chromosome 5 is associated
with Cri du chat syndrome – a genetic disorder unrelated to MDS,
named due to the characteristic cat cry made by affected children
(‘cri du chat’ from French meaning ‘call of the cat’).

1012
Q

It affects children and teenagers and has a characteristic chromosomal
translocation (t11;22)(q24;q12). It is negative for alkaline phosphatase
and positive for CD99 (MIC2) immunostain. It is more commonly found
in the pelvis and diaphysis/metaphysis of long bones than around the
knee. Widespread metastases and bone marrow involvement are frequent.

A

Ewing’s sarcoma

1013
Q

usually affect older patients. The prognosis is variable
depending on the grade of tumour. They usually grow slowly and
not only affect long bones but also the ribs, spine and pelvis. The only
treatment is surgical
excision as both chemotherapy and radiotherapy are
ineffective.

A

Chondrosarcoma

1014
Q

are both spindle cell malignant tumours, arising from stromal cells and
collectively they make up the majority of soft tissue sarcomas

A

Fibrosarcomas and malignant fibrous histiocytomas

1015
Q

The most common presentation is pain and a mass, which occurs
near a joint such as the knee, with the distal femur and proximal tibia
being the most common sites. X-rays show a mixed sclerotic and lytic
lesion in the metaphysis that may permeate the bone causing a soft tissue

mass and a periosteal reaction. Bone formation within the tumour is characteristic
of osteosarcoma and is usually visible on X-rays. Bone alkaline
phosphatase has significant value in diagnosing

A

Osteosarcoma

1016
Q

is
a form of fibrosing lung disease that is chronic and progressive. It presents
with shortness of breath and cough and is more likely to be seen in males
over the age of 50. On histopathology, fibrosis and cyst formation are seen.

A

Cryptogenic fibrosing alveolitis

1017
Q

These tumours, if well-differentiated, show keratin
pearls and cell junctions (or desmosomes), which form the characteristic
intercellular ‘prickles’.

A

Squamous cell carcinoma

1018
Q

has a very close association with smoking
and paraneoplastic
syndromes and is very chemo-sensitive. They are poorly differentiated
and the mutations commonly involved are p53 and RB1.

A

SCLC

1019
Q

is a type of fibrosing lung disease or
‘dusty lung’ caused by inorganic dust inhalation. It commonly affects the
upper lobes, while asbestosis affects the lower lobes more severely. It is
an alteration of the lung structure rather than neoplastic differentiation of
cells and is therefore unlikely to be the diagnosis for this patient.

A

Pneumoconiosis

1020
Q

is a benign lesion that is rapidly growing and
dome-shaped. It arises from the pilosebaceous glands and often resembles
SCC. However, the growth of a keratoacanthoma retains its smooth
surface, unlike an SCC and a malignant melanoma.

A

Keratoacanthoma

1021
Q

presents as an enlarging well-demarcated erythematous plaque with an
irregular border but non-elevated.

A

Bowen’s disease

1022
Q

of the
skin begins as a small nodule that may become ulcerated and necrotic.
Bleeding is quite common and the clinical presentation is highly variable.

A

SCC

1023
Q

histopathology is spongiosis of epidermis and
perivascular chronic inflammatory infiltrate in the dermis. Acanthosis
(epidermal thickening) would develop if xx becomes chronic.

A

Eczema

1024
Q

will commonly present with
psoriatic nail lesions (pitting, onycholysis), dactylitis and tendinitis.
X-rays will show ‘new fluffy’ bone.

A

Psoriatic arthritis

1025
Q

a rheumatoid factor-seronegative, HLA B27-linked spondyloarthopathy
commonly affecting the larger joints (e.g. sacroiliac and
knee joints). Patients also sometimes develop circinate balanitis, keratoderma
blenorrhagica and enthesitis of the Achilles tendon

A

Reiter’s syndrome (Reactive arthritis)

1026
Q

Macroscopically, the
kidney is replaced by rounded masses of solid, fleshy, white lesions
with vast amounts of necrosis. Microscopically, it is composed of four
elements: immature-looking glomerular structures, primitive small cell
blastaematous tissue, epithelial tubules and stroma composed of spindle
cells and striated muscle.

A

Wilm’s

dWT1

1027
Q

is a benign epithelial tumour composed of large cells
with granular, eosinophilic cytoplasm filled with mitochondria. It has
little necrosis or haemorrhage. It is a variant of renal adenoma and is
often confused with renal cell carcinoma.

A

Oncocytoma

1028
Q

Only xx papillomas can present with nipple discharge that is blood
stained, while xxl papillomas can remain clinically silent.

A

Central

Peripheral

1029
Q

is a
benign sclerosing lesion characterized by a central zone of scarring surrounded
by a radiating zone of proliferating glandular tissue. They are
common and usually present as stellate masses on screening mammograms.

A

Radial scar

1030
Q

B1 to B5b grading

A
  • B1 = normal breast tissue.
  • B2 = benign abnormality (A)
  • B3 = lesion of uncertain malignant potential (B)
  • B4 = suspicious of malignancy (E)
  • B5 = malignant
  • B5a = ductal carcinoma in situ (C)
  • B5b = invasive carcinoma
1031
Q

is a failure of
differentiation of metanephric tissues, it is typically asymptomatic and
it is not hereditary in nature but developmental, therefore often presenting
in childhood.

A

Cystic renal dysplasia

1032
Q

is occasionally a familial condition that
does not impair renal function and presents with renal stones predisposing
to renal colic and infections.

A

Medullary sponge disease

1033
Q

Meningitis in people with surgical shunts

A

Staph aureus and gram negative rods are the most comon cause