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Flashcards in Haematology Deck (188):
1

What infection is assocaited with hodgkin lymphoma?

Epstein barr virus

 

(also more common in people with HIV)

2

What is the treatment for neutropenic sepsis?

Administer high flow oxygen

Take blood cultures, other cultures, consider source control

Give appropriate IV antibiotics within ONE hour

Measure serum lactate concentration

Start IV fluid resuscitation 

Assess/measure urine output

 

Resuscitation – ABC

Broad spectrum I.V. antibiotics

- Tazocin and Gentamicin

If a gram positive organism is identified add vancomycin or teicoplanin

If no response at 72 hours add I.V. antifungal treatment e.g. Caspofungin - empiric therapy

CT chest/abdo/pelvis  to look for source

Modify treatment based on culture results

3

What is the most common blood group?

Type O

4

What mutation is assocaited with primary Myelofibrosis?

JAK2 (50%)

MPL (5-10%)

5

What is the treatment for 22q11 deletion syndrome?

Thymus transplantation

6

What is the role of platelets in haemostasis?

Adhere

Activate

Aggregate

Provide a phospholipid surface for coagulation

7

What is the cause of polycythaemia rubra vera?

Clonal proliferation of a marrow stem cell leading to an increased red cell volume, often accompanied by an increase in neutrophils and platelets as well

8

What are different types of venous thromboembolisms?

Limb deep vein thrombosis

Pulmonary embolism

Visceral venous thrombosis

Intracranial venous thrombosis

Superficial thrombophlebitis

9

What type of monoclonal proteins are usually found in the serum in multiple myeloma?

IgG or IgA 

10

What are the symptoms of hereditary spherocytosis?

Anaemia

Jaundice (neonatal)

Splenomegaly

Pigmented gallstones

11

What is the treatment for chronic lymphocytic leukaemia?

Often nothing – “watch and wait”

Cytotoxic chemotherapy e.g. fludarabine, bendamustine

Monoclonal antibodies e.g. Rituximab, obinutuzamab

Novel agents (these are targeted therapies)

Bruton tyrosine kinase inhibitor eg ibrutinib

(think of Brutus on a tyrosine kinase inhibitor)

PI3K inhibitor eg idelalisib

(Think of Pie eaten by KKK)

BCL-2 inhibitor eg venetoclax

(Think of a female venus on Jeremy Clarkson)

12

What is the managment of TRALI?

Stop transfusion immediately and follow other steps for managing suspected transfusion reactions.

Provide cardiovascular and airway support. Administer supplemental oxygen and employ ventilation as necessary. Diuretics are not beneficial.

13

How is the diagnosis of multiple myeloma made?

X-ray - lytic bone lesions of the skull, long bones and the spine

CT scan - radiodense bone lesions and lesions found in the spleen, lymph nodes and lungs as a result of chronic disease

MRI

FISH (fluorescent in situ hybridisation)

LAB results: leukopenia, thrombocytopenia, creased monoclonal proteins, bence jones proteins, raised calcium

Bone marrow biopsy - over 30% plasma cells

14

What are the platelets like in myelofibrosis?

Platelets are increased, abnormally shaped and they have decreased survival

15

What are poor prognostic indicators for chronic lymphocytic leukaemia?

Advanced disease (Binet stage B or C)

Atypical lymphocyte morphology

Rapid lymphocyte doubling time (<6 mth), or over 50% increase in less than 2 months

CD 38+ expression

Loss/mutation p53; del 11q23 (ATM gene) - p53 is a tumour suppressor gene - loss in this is a bad prognostic indicator for ANY cancer pretty much - good tip for exams to include this as an answer.

Unmutated IgVH gene status

Raised LDH (lactate dehydrogenase - this is a measure of haemolysis)

Male Sex

Age over 70

Lymphocyte count over 50

 

I think another poor prognostic indicator would be mutation on short arm of chromosome 17 as opposed to the long arm of 13

16

Who gets acute lymphoblastic leukaemia?

Ususally children less than 6 years of age

17

How do innate immune diosrders present?

Defects in phagocyte funtion

(staph aureus, sepsis, skin lesions, abscesses internal organs)

(Aspergillus infections (lung, bones, brain)

(Complement deficiencies)

N, Meningitidis

18

Why does the liver and spleen get bigger in primary myelofibrosis?

As a result of myeloid metaplasia

Liver and spleen start making haematopeitic stem cells

19

What are the vitamin K dependant factors?

4,7,9,10

 

Warfarin reduces the amount of these factors

20

What is the treatment of hereditary angiodema?

Acute managment of pharyngeal / laryngeal obstruction

Acute abdominal pain

 

Requires C-1 inhibitor infusion OR fresh frozen plasma

21

Red cell donor table

22

What are poor prognostic factors for acute lymphoblastic leukaemia?

Poor prognosis factors:

 

Increasing age

Increased white cell count

Immunophenotype (more primitive forms)

Cytogenetics/molecular genetics

t(9;22); t(4;11)

t(9;22) is the philidelphia chromosome I think

Slow/poor response to treatment

 

23

What is the error in haemoglobin for sickle cell and thalassaemia?

Sickle cell = abnormal haemoglobin

Thalasaemia = 

24

What mediates immediate tissue rejection?

Immediate rejection is mediated by ABO/HLA antibodies and compliment activation which damages blood vessels (rapid intravascular thrombosis and necrosis)

25

What is the presentation of acute leukaemia?

Thrombocytopenic bleeding (Purpura and mucosal membrane bleeding). Petechial bleeding that is non blanching. 

- Infection because of neutropenia (predominantly bacterial and fungal) e.g cellulitis

 - Bone marrow failure - there is a complete replacement of bone marrow with blast cells. These cells are undifferentiated. 

26

What are investigations for chronic lymphocytic leukaemia?

Blood count : lymphocytosis (over 5000 per mm3), thrombocytopenia

Bone marrow is over 30% lymphocytes

Loss of immunoglobulin production

Haemolytic anaemia

Smudge cells on blood film

Immunophenotyping

 

27

What is the diagnostic test for G6PD deficiency?

G6PD enzyme assay

28

What is the cause of death in myelofibrosis?

Death is usually due to bone marrow failure (haemorrhage, anaemia, or infection), transformation to acute leukaemia, portal or pulmonary hypertension, heart failure, cachexia, or myeloid metaplasia with organ failure.

29

What is the presentation of acute myeloid leukaemia?

- Anaemia (SOB, fatigue, pallor)

- Thrombocytopenia (bruising, petechiae, epistaxis)

- Neutropenia (bacterial infections, pneumonia, sepsis)

 

Neoplastc infiltration:

- Bone marrow (bone pain)

- Thymus (palpable mass/airway compression)

- Liver and spleen (hepatosplenomegaly)

- Lymphadenopathy

- Headaches, vomitting, nerve palsies, nuchal rigidity

 

Can also cause gum swelling which is classic for acute myeloblastic leukaemia

30

What is the character of the lymphadenopathy found in lymphoma?

Painless and typically has a rubbery feeling. If it were metastatic cancer from the lung it would typically feel very hard.

31

How do we prevent graft rejection?

Treatment of rejection:

 

Corticosteroids

Anti-thymocyte globulin

Plasma exchange

 

Prevention of graft rejection:

ABO matching

Tissue typing (class 1 and 2 HLA)

Prophylactic immunosuppression

 

Immunosuppression:

Corticosteroids (prednisolone)

Calcineurin inhibitors (tacrolimus) - blocks interleukin 2 gene transcription

Antiproliferatives (MMF) (mycophenolate mofetil) - these prevent lymphocyte proliferation

32

What are causes of iron deficiency anaemia?

Menorrhagia

Dyspepsia

PR bleeding

Symptoms of malabsorption (diarrhoea, weight loss)

Jaundice

Splenomegaly

33

What are the indications of platelet transfusion?

Massive haemorrhage

Bone marrow failure

Prophylaxis for surgery

Cardiopulmonary bypass

34

What is the cause of factor V leiden?

 

Increases chances of VTE

mis-sense mutation is that activated factor V (a clotting factor) is inactivated 10 times more slowly by activated protein C than normal

35

What mediates acute tissue rejection?

Acute rejection is mediated by cell and antibody defences. Cellular infiltration of graft by Tc cells, B - cells, NK cells and Macrophages. Causes endothelial inflammation and parenchymal damage.

36

What is the presentation of essential thrombocytosis?

Characteristic symptom is a burning sensation in the hands

 

Thrombosis (venous or arterial) and haemorrhage can be seen.

 

Symptoms of arterial and venous thromboses, digital ischaemia, gout, headache

 

Mild splenomegaly

37

What is the time period recquired for immedaite tissue rejection, acute tissue rejection and chronic tissue rejection?

Immediate rejection = within minutes

Acute rejection = less than 6 months

Chronic rejection = more than 6 months

38

What are the two types of haemolysis seen in normocytic anaemia?

Immune is mosty extravascular

Non-immune is mostly intravascular 

39

What is the cause of essential thrombocytopenia?

Megakaryocyte proliferation results in an overproduction of platelets.

 

40

What are exmamples of warm antibody?

Autoimmune

Drugs

CLL

41

What is the mechanism of G^PD deficiency?

 

↓ G6PD → ↓ glutathione → increased red cell susceptibility to oxidative stress

42

What are hallmarks for primary myelofibrosis?

Leukoerythroblastosis and splenomegaly

Splenomegaly happens as a result of extra medullary haematopoeisis

 

Trephine biopsy shows an excess of megakaryocytes, increased reticulin and fibrous tissue replacement

Presence of a JAK2 mutation supports the diagnosis

43

What are the symptoms of TRALI?

Acute onset of fever, chills, dyspnoea, tachypnoea, tachycardia, hypotension, hypoxaemia and noncardiogenic bilateral pulmonary oedema leading to respiratory failure during or within 6 hours of transfusion.       (shock picture)

44

What are the B cell markers found on immnophenotyping?

CD19, 20 and 23 and CD5 positive

CD19 and 20 are common markers to which we target therapy

45

Prognosis for acute lymphoblastic leukaemia?

Prognosis:

Adults with ALL 

complete remission rate         78–91%

leukaemia-free survival at 5y     30–35%

Children with ALL

5y overall survival             ~90%

Poor risk patients (slow response to induction or Philadelphia positive) 5y OS    45%

(most children survive, half of adults survive)

46

What are the symptoms of TACO?

(transfusion associated circulatory overload)

Acute respiratory distress

Tachycardia

Raised blood pressure

Acute worsening pulmonary oedema on CXR

Evidence of positive fluid balance

Orthopnea

 

(shortness of breath, peripheral and pulmonary oedema, high blood pressure)

47

What causes chronic lymphocytic leukaemia?

Monoclonal proliferation of mature functionally abnormal B cells, these mature B lymphocytes accumulate in the bone marrow - physical suppression, prevents maturation

48

How does sickle cell disease present?

Painful criris

Stroke

Gallstones

 

Chest crisis:

- Chest pain

- Fever

- Worsening hypoxia

49

Why might factor 8 be reduced in von willebrands disease?

Von willebrand factor is a carrier molecule of factor 8

50

How do innate immune disorders arise?

Defects in phagocyte function

Complement deficiencies

Absence or polymorphisms in pathogen recognition receptors

51

What causes hereditary angiodema?

Caused by a C1 inhibitor deficiency

Autosomal dominant

52

What are the treatments available for primary myelofibrosis?

Low risk for thrombosis

Antiplatelet drugs (aspirin, anagrelide)

High risk for thrombosis

Hydroxyurea, interferon-alpha

Folate to prevent deficiency

 

Ruxolitinib is a JAK2 inhibitor that has recently been licensed for use

 

Haematopoietic stem cell transplant is the only treatment option with a potential for cure.

53

What is the treatment for haemolytic anaemia?

Treatment for haemolytic anaemia 

Support marrow function

–Folic acid

Correct cause

–Immunosuppression if autoimmune

•Steroids

•Treat trigger eg.CLL, Lymphoma

–Remove site of red cell destruction

•Splenectomy

–Treat sepsis, leaky prosthetic valve, malignancy etc. if intravascular

Consider transfusion

 

Causes for haemolysis:

autoimmune - give steroids / immunosuppressants

DRUGS
CLL - treat

 

CHAD

Infections - treat sepsis

 

(so basically, give steroids if autoimmune, treat any infections and cancers)

54

What are the types of macrocytic anaemia?

Megaloblastic = vitamin B12 and folate

Normoblastic =

  • Alcohol
  • Liver disease
  • Hypohyroidism
  • Pregnancy
  • Reticulocytosis
  • Myelodysplasia
  • Cytotoxic drugs

55

What is the treatment of chronic myeloid leukaemias?

Tyrosine kinase inhibitors

 

Says to not give blood - will exacerbate hyperviscosity (I think this is in respect to tumour lysis syndrome)

56

What is the investigation for sickle cell disease?

Lab results:

- Target cells

- Reticulocytosis

- Increased WBC

Evidence of haemolysis (increased unconjugated bilirubin, increased lactate dehydrogenase, decreased haptoglobin)

Haemoglobin electrophoresis = definitive diagosis

57

What is the diagnosis of acute lymphoblasic leukaemia?

Blood count - increased WBC, increased lymphoblasts

Bone marrow smear (hypercellular bone marrow, lymphoblast domination)

Immunophenotyping - Terminal deoxynucleotidyl transferase (TdT) is a marker found in premature T and pre-mature B lymphoblasts that is used to diagnose acute lymphoblastic leukemia.

 

58

What is the effect of cellular immunodeficiency?

Unusual or opportunistic infections often combined with failure to thrive

pneumocystis jirovecii

CMV

59

What is the cause of sickle cell disease?

Point mutation in the beta globin gene

Produces haemaglobin S (HbS) - these cells containing HbS tend to crescent chapes when they are deoxygenated

 

They have one normal and one abnormal beta globin chain

60

What antibodies are present in A group blood?

Antibodies against type B blood

61

Note on 22q11

Most common microdeletion syndrome

Incidence is higher in those with down’s syndrome

 

2nd most common cause of developmental delay and major congenital heart disease

62

What is the treatment of hodgkin lymphoma?

Combination chemotherapy (ABVD)

+/- radiotherapy

Monoclonal antibodies (anti-CD30)

Immunotherapy (checkpoint inhibitors)

Use of PET scan to assess response to treatment and to limit use of radiotherapy

 

Rituximab an be used as well

63

What are the different types of acute lymphoblstic leukaemia?

Composed of T cell precursors or B cell precursors

 

These cells are stuck in the blast phase (undifferentiated)

Divide uncontrollably - take up a lot of space and nutrients in the bone marrow - cytopenias (anaemia, thombocytopenias, leukopenias)

64

What is responsible for fibrinolysis?

Plasmin

65

What are the blood findings in tumour lysis syndrome?

High potassium

High phosphate

Low calcium

High uric acid

High urea and nitrogen containing compounds

66

What are the different types of von wilebrand disease?

Type 1 = quantitive deficiency (80% of patients)

Type 2 = qualititive deficiency

Type 3 = severe (complete) deficiency

67

How does myeloma affec tthe kidneys?

Small molecular weight molecules can pass through the glomerulus - bence jones protein in the urine - causes proximal tubular necrosis

Cast nephropathy

Nephrocalcinosis as a result of hypercalciuria

Free light chains deposit in the kidneys, heart and other organs - causing AL amyloidosis 

68

What is the most common cause of death in patients with sickle cell disease?

URTI

69

What type of blood should you give in emergencies? (minutes)

O RhD neg red cells  (AB plasma)

70

Who gets G6PD deficiency?

It is X linked recessive so Males

Common in people from mediterranean and africa

 

71

What is the treatment for essential thrombocytosis?

hydroxyurea (hydroxycarbamide) is widely used to reduce the platelet count

Anagrelide

interferon-α is also used in younger patients

low-dose aspirin may be used to reduce the thrombotic risk

72

What are the complications of chronic lymphocytic leukaemia?

Abnormal Ig secretion (hypogammaglobulinaemia, autoimmunity)

Richter syndrome- can progress to aggressive lymphoma (large B cell lymphoma)

73

What is the presentation of anaemia?

General features due to reduced oxygen delivery to tissues:

  Tiredness/pallor

  Breathlessness

  Swelling of ankles

  Dizziness

  Chest pain

 

Potential History:

–Dyspepsia  GI bleeding

–Other bleeding, eg menorrhagia

–Diet (NB children and elderly)

Increased requirement - pregnancy 

Malabsorption from gastrectomy and coeliacs

 

Atrophic tongue

Angular Chelitis

Hypochromic, microcytic cells 

Koilonychia

 

B12/folate deficiency = anaemia, neurological symptoms (subacute combined degeneration of the cord in B12 deficiency.)

 

Megaloblastic anaemia:

“Lemon yellow” tinge

–Bilirubin, LDH

–Red cells friable

74

What is the investigation for acute lymphoblastic leukaemia?

Low haemoglobin

Raised WCC  (this is incontrast to myeloma which has leukopenia)

Low platelets

Bone marrow (90% B - Lymphoblasts)

75

What is the presentation for polycythaemis rubra vera?

Incidence peaks in the 6th decade

hyperviscosity (stroke, vascular occlusion, thrombosis, TIA)

pruritus, typically after a hot bath

splenomegaly

haemorrhage (secondary to abnormal platelet function)

plethoric appearance

hypertension in a third of patients

 

Symptoms of hyperviscosity include loss of concentration, headaches, dizziness, blackouts, pruritis and epistaxis

76

What are some of the complications of sickle cell disease?

Aplastic crisis (temporary arrest of erythropoeisis, can be caused by parovirus B19)

Vaso-occlusion, tissue ischaemia and infarction

Daytylitis

Hyposplenism means increase risk of infection

MI

VTE

Dysrhythmias

Acute chest syndrome (fever, chest pain, hypoxemia, wheezing, cough, respiratory distress)

Pulmonary hypertension

Osteoporosis

Proliferative retinopathy

Multi-organ failure

Priapism

77

What is the point in the coombs test?

Tests for auto immune haemolytic anaemia

Used to detect antibodies or compliment proteins attached to red cells

 

f the red cells then agglutinate, the direct Coombs test is positive, a visual indication that antibodies or complement proteins are bound to the surface of red blood cells and may be causing destruction of those cells.

78

What does megaloblastic mean? 

Impairment of DNA synthesis, cell cycle cannot progress from G2 growth stage to the mitosis stage - continued cell growth without division

79

What is the presentation of primary myelofibrosis?

Massive splenomegaly

Fatigue

Erythromelalgia

constitutional symptoms (weight loss, night sweats, low-grade fever, cachexia, fatigue, and pruritus)

 

80

What is staging of chronic lymphcytic leukaemia?

Binet staging

81

What are causes of ITP?

EBV

HIV

Collagenosis

Lymphoma

Drug induced (quinine)

82

What clotting factor is reduced in Haemophilia type A and type B?

A = factor 8

B = factor 9

83

What are the causes of microcytic anaemia?

Iron deficiency anaemia

Thalassaemia

Congenital sideroblastic anaemia

Lead poisoning

Anaemia of chronic disease (although this is more commonly a normocytic picture)

84

What antibodies are present in O type blood?

Antibodies against A and B

85

What casues primary myelofibrosis?

Proliferation of myeloid haematopoetic stem cells

Overproduction of megakaryocytes in the bone marrow leading to bone marrow fibrosis

86

What are the types of non-hodgkine lymphoma?

Burkitt (very aggressive)

Diffuse large B cell (aggressive) - most common subtype of lymphoma
Extranodal marginal zone MALT - slow growth

Follicular (slow growth) - 2nd most common subtype

 

Low grade lymphoma - indolent, often asymptomatic, responds to chemotherapy but is itself incurable

 

HIgh grade - aggressive and fast growing, can be cured

87

What is the mechanism of disease in acute myeloid leukaemia?

Neoplastic monoclonal proliferation of myelogenous stem cells (myeloblasts) in bone marrow

 

Immature myeloblasts accumulate in

bone marrow

physical suppression

prevents maturation

88

Where does the structural abnormality lie in hereditary spherocytosis?

Defect in the cytoskeleton in red blood cells

 

Red blood cell survival is reduced due to destruction by the spleen

89

What is diagnosis of venous thrombosis?

Pretest probability scoring

Wells score

Geneva score

Laboratory testing if pretest probability low

D-dimer

Imaging

Doppler US - compression ultrasonography, contrast venography, CT venography, MRA

DVT thrombosed vein enlarged, non-compressible, echogenic material might be seen

 

Ventilation perfusion scan

CT pulmonary angiogram

90

What type of blood do we give in non-urgent scenarios?

Full cross match

ABO / RhD specific

Choose antigen negative blood if there are alloantibodies

91

What might precipitate a haemolytic crisis in G6PD deficiency?

Infection

Fava beans

Drugs (NSAIDs, aspirin, nitrofurantoin, quinine)

92

What is the essential investigation if there is a macrocytic picture?

Folate/B12 + bone marrow

93

What are risk factors for stasis/hypercoagulability?

Increasing age

Pregnancy

Surgery

Obesity

Systemic disease

Family history

Tissue trauma

Immobility

Hormonal therapy (COCP/HRT)

COCP = combined oral contraceptive pill

Antipsychotics

94

What is the treatment of megaloblastic anaemia?

Treatment for megaloblastic anaemia:

Replace vitamin

B12 deficiency

–B12 intramuscular injection

–Loading dose then 3 monthly maintenance

 

Folate deficiency

–Oral folate replacement

–Ensure B12 normal if neuropathic symptoms

95

Why is screening for factor v leiden not indicated?

Screening for factor V Leiden is not recommended, even after a venous thromboembolism. The logic behind this is that a previous thromboembolism itself is a risk factor for further events and this should dictate specific management in the future, rather than the particular thrombophilia identified.
 

96

What is the treatment for iron deficiency anaemia?

Correct the deficiency -

  Oral iron usually sufficient

  IV iron if intolerant of oral

  Blood transfusion rarely indicated

Correct the cause -

  Diet

  Ulcer therapy

  Gynae interventions

  Surgery

97

What are examples of cold antibody haemolysis?

CHAD

Infections

Lymphoma

98

What is treatment for haemophilia?

•Coagulation factor replacement  FVIII/IX

•Now almost entirely recombinant products

•DDAVP (desmopressin) (this can be used in patients with haemophilia A, von willebrand disease and thrombocytopenia, cannot be used for haemophilia type B. The drug works by increasing the amount of von willebrand factor and factor 8.

•Tranexamic Acid

•Emphasis on prophylaxis in severe haemophilia

•Gene therapy?

•Splint

•Physiotherapy

•Analgesia

•Synovectomy

•Joint replacement

 

Treatment is designed to get the person to the point where they are no longer severely haemophilic (we want to make sure they no longer bleed spontaneously which is the definition of severe)

99

What is the role of von willebrand factor?

Promotes platelet adhesion to damaged endothelium

100

Why is prothrombin time different to activated partial thromboplastin time?

PTT = intrinsic pathway (intrinsic pathway contains factor 8 and 9)

PT = extrinsic pathway

101

What is managment of b=von willebrands disease?

tranexamic acid for mild bleeding

desmopressin (DDAVP): raises levels of vWF by inducing release of vWF from Weibel-Palade bodies in endothelial cells

factor VIII concentrate

VW factor concentrate

102

What is prognosis for chronic lymphocytic leukaemia?

Median survival:

Stage A - same as matched controls

Stage B - around 8 years

Stage C = around 6 years

103

What are the features of multiple myeloma?

Clinical features

bone disease: bone pain, osteoporosis + pathological fractures (typically vertebral), osteolytic lesions

lethargy

infection

hypercalcaemia 

renal failure

other features: amyloidosis e.g. Macroglossia, carpal tunnel syndrome; neuropathy; hyperviscosity (hyperviscosity syndrome caused by malignant cells producing lots of paraproteins)

 

Bleeding tendancy (retinal, oral, nasal or cutaneous)

104

What are the causes of DIC?

Septicaemia

Malignancy (acute myeloid leukaemia can cause DIC)

Eclampsia

105

What is the presentation of hodgkin lymphoma?

lymphadenopathy (75%) - painless, non-tender, asymmetrical

systemic (25%): weight loss, pruritus, night sweats, fever (Pel-Ebstein)

alcohol pain in HL

normocytic anaemia, eosinophilia

LDH raised

106

Note on multiple myeloma

Its a neoplastic disorder of plasma proteins that usually results in the excessive production of a single type of immunoglobulin (paraprotein)

 

Peaks in 7th decade

 

More common in black people than white.

107

How does hereditary angiodema present?

Recurrent episodes of painless, non-pitting, non-pruritis, non-erythematous swellings

Swellings can be:

- Subcutaneous

- Intestinal 

- Oropharynx

108

What type of blood should we give in urgent scenarios?

ABO / RhD specific

109

What is the managment for arterial clots?

Thromolysis

Antiplatelet/anticoagulant drugs

110

What structural defects cause hereditary spherocytosis?

Ankyrin

Alpha spectrin

Beta spectrin

Band 3 

Protein 4.2

111

Who gets hodgkin lymphoma?

 It has a bimodal age distributions being most common in the third and seventh decades

112

What causes severe combined immunodeficiency?

Cytokine receptor defects are the most common cause - most commonly adenosine deaminase deficiency - low levels of this enyme result in a decline of T cells and B cells

113

What are causes of normocytic anaemia?

Chronic kidney disease

Haemolytic anaemia

Aplastic anaemia

Anaemia of chronic disease

114

What is the treatment for multiple myeloma?

Chemotherapy

Immunomodulators such as thalidomide

Proteasome inhibitors, IMiDs, monoclonal antibodies

Bisphosphonate therapy (Zoledronic acid) - these prevent bone loss

Radiotherapy

Steroids

Surgery

Pinning of long bones; decompression of spinal cord

Autologous stem cell transplant

Antibiotics to treat infections

115

What is th ehallmark feature of PV?

Iron deficiency 

You don't give iron because that will cause a stroke

116

What causes beta thalassaemia major?

Absence of beta chains 

Chromosome 11

117

What are the symptomsof hypercalcaemia associated with Multiple Myeloma?

Thirst

Constipation

Solomnence

Confusion

Nausea

118

What are investigations for chronic myeloid leukaemia?

Blood count shows increased granulocytes (basophils, eosinophils and neutrohpils)

Bone marrow biopsy shows hypercellularity (cells of myeloid cell line / precursors)

 

FISH/PCR for karyotypic analysis: BCR-ABL 1 gene mapping

 

Small chromosome 22 = philidelphia chromosome. Small chromosome is the result of balanced translocation with chromosome 9. You are left with a small 22 and a BCR - ABL on 22 - this then results in an increased amount of ABL.

119

What is the treatment of acute lymphblastic leukaemia?

Chemotherapy 

Consolidation therapy

Maintenance treatment 

Stem cel transplant if high risk

Large portion of care is to ensure children continue to grow and develop - keep up with school etc

CNS directed therapy (chemotherapy doesn’t penetrate well and it often spreads to the CNS) - give medicines intrathecally by lumbar tap or lumbar puncture

Maintenance treatment for 18 months

Bone marrow transplant in those that are likely to relapse

 

Newer therapies:

1) Bispecifc T-cell engagers (BiTe molecules) – e.g. Blinatumumab - draws t cells to cancerous cells to destroy the cancer

2) CAR (chimeric antigen receptor T-cells)

Patient/ healthy 3rd party T-cells harvested

Transfected to express a specific T-cell receptor expressed on leukaemia cells (CD19)

Expanded in vitro

Re-infused into patient

CAR - T cells have risk of cytokine release syndrome - signs include fever, hypotension and dyspnoea

120

What is the treatment for hereditary spherocytosis?

Folci acid

Transfusion

Splenectomy

121

What are potential side effects from transfusion?

Febrile non-haemolytic transfusion reaction

TACO

TRALI

Allergic

Transfusion assocaited graft vs host disease

Prion disease such as CJD

 

122

What is the treatment of PV?

Venessection to keep the haematocrit below 0.45 and 0.43 in women

Aspirin

Hydroxycarbamide

Ruxolitinib - JAK 2 inhibitor

Interferon alpha

123

What is the essential test if there is hypochromic and microcytic anaemia?

Need to do serum ferritin, reduced serum ferritin means iron deficiency anaemia

If male you might want to do a GI endoscopy to check for bleeding

124

How is the diagnosis of acute myeloid leukaemia made?

Blood count will show leukocytosis and anaemia

 

Bone marrow aspirate (over 20% of the cells withh be myeloblasts)

 

Myeloblasts containing Auer rods

 

Others:

- Immunophenotyping of leukaemic blasts (remember that acute lymphoblastic will contain terminal deoxynucleotidyl transferase)

- CSF examination if there are symptoms

125

What can PV beceom

AML

126

What are the relevant investigations for multiple myeloma?

- IgG, IgA paraproteins - these are produced by mature plasma cells after isotype switching

127

What are the characteristics of the hodgkin lymphoma cell?

Presence of reed-sternberg cells

Giant B cells with bilobed nuclei that have prominent eosinophilic inclusions

128

What is the presentation of beta thalassaemia major?

Failure to thrive

Hepatosplenomegaly

Bony deformities

Growth retardation

129

What does myelodysplastic syndromes become?

bone marrow failure or AML

 

HSTC is the only curative option

130

What activates platelets?

Abnormal surface or physiological activator

131

What is the treatment for sickle cell disease?

Life long prophylaxis

–Vaccination

–Penicillin (and malarial) prophylaxis 

–Folic acid

 

Acute Events

–Hydration

–Oxygenation

–Prompt treatment of infection

–Analgaesia

•Opiates

•NSAIDs

 

Blood transfusion

–Episodic and chronic

–Alloimmunisation

–Iron overload

 

Disease modifying drugs

Hydroxycarbamide - this increases the amount of fetal haemoglobin in the blood and so therefore decreases the number of crisis'

- L glutamine - duces sickling

Bone marrow transplantation

Gene therapy

 

Treatment for painful crisis:

 

•Severe pain- often requires opiates

  -Analgesia should be given within 30 mins of presentation

  -Effective analgesia by 1hour

  - Avoid pethidine

•Hydration

•Oxygen

•Consider antibiotics

No routine role for transfusion  

 

 

Treatment for a chest crisis:

Respiratory Support

Antibiotics

IV Fluids

Analgaesia

Transfusion – top up or exchange target HbS <30%     

132

What is the managment of beta thalassaemia major?

Repeated blood transfusions

To prevent iron overloading you have to use a chelation therapy

s/c desferroxamine is gold standard - oral alternative is deferasirox

Bone marrow transplant = curative

133

What are the main risks assocaited with PV?

Cerebrovascular or coronary events occur in up to 60% of patients. The disease may convert to another myeloproliferative disorder with about 25% developing acute leukaemia or myelofibrosis

134

What parts of the platelets are responsible for the following functions?

Adhering

Activating

Aggregating

Coagulation

Involved in adherence = GP 1b and GP 1a

 

Involved in activation = ADP and COX

 

Involved in aggregation = thromboxane A2

 

Involved in coagulation = scramblase

135

What are indications for red cell transfusion?

Correct anaemia which may cause organ damage if left uncorrected

To improve quality of life in a patient with otherwise uncorrectable anaemia

To prepare a patient for surgery or to speed up recovery

To reverse damage caused by patients own red cells

136

How do antibody deficiencies normally present?

Recurrent bacterial infections of the upper and or lower respiratory tract

 

S.pneumoniae

H.influenzae

137

What is the investigation for hereditary spherocytosis?

DAT - not an immune reaction therefore there is a negative result

 

No tests necessary if there is a family history, typica clinical features and typical lab findings (spherocytes, raised MCHC, raised reticulocytes)

Cryohaemolysis test and EMA binding

138

What is the investigations for polycythaemia vera?

Raised haemoglobin concentration and haematocrit

Tendancy to also have a raised white cell count and platelet count

Raised uric acid since there is an increased cell turnover

Increase in red cell mass when the blood volume is measured

 

Presence of JAK2 mutation - in JAK 2 negative cases you have to rule out secondary causes of erythrocytosis

139

What is the presentation of haemophilia?

•Haemarthrosis

•Muscle haematoma

•CNS bleeding

•Retroperitoneal bleeding

•Post surgical bleeding

 

Complications can include:

Synovitis

Chronic Haemophilic Arthropathy

Neurovascular compression (compartment syndromes)

Other sequelae of bleeding (Stroke)

140

What are the natural anticoagulants?

Protein C

Protein S

TFPI (tissue factor pathway inhibitor)

Antithrombin

 

These confine the clot to the area of tissue damage

141

What is therapy for non-hodgkin lymphoma?

Both are treated with combination chemotherapy

 

Both are treated with combination chemotherapy – typically anti-CD20 monoclonal antibody + chemo

CD20 monoclonal antibody is rituximab

142

What is the bleeding pattern of von Willebrands disease?

Behaves like a platelet disorder i.e. epistaxis and menorrhagia are common whilst haemoarthroses and muscle haematomas are rare

143

How do antibody deficiencies arise?

Defective B cell function

Absence of mature B cells

144

What causes B12 deficiency?

Pernicious anaemia, caused by gastric / ileal disease

Antibodies against intrinsic factor (diagnostic)

Gastric parietal cells (less specific)

Malabsorption of dietary B 12

Symptoms / signs take 1-2 years to develop

 

produced by the parietal cells of the stomach. It is necessary for the absorption of vitamin B12 later on in the ileum of the small intestine.

145

What are systemic symptoms of lymphoma?

Fever

Drenching sweats, loss of weight, prutitis, fatigue

B symptoms: fever, drenching sweats, 10% non-deliberate weight loss, fatigue, pruritis

 

 

High grade makes you feel ill very quickly - not usually found by accident

 

Low grade grows slowly and are often found by accident

146

What are relecant investigations for neutropenic sepsis?

History and examination

Blood cultures    -Hickman line & peripheral

CXR

Throat swab & other clinical sites of infection (if UTI do MSSU)

Sputum if productive

FBC, renal and liver function, coagulation screen

147

What is the presentation of G6PD deficiency?

Neonatal jaundice (like HS)

Drug, borad bean or infection precipitated jaundice and anaemia (haemolysis)

Intravascular haemolysis (HS is extravascular)

Splenomegaly

Pigment gallstones

148

What are chromosonal changes assocaited with chronic lymphocytic leukaemia?

Chromosomal Changes:

Deletion of the long arm of chromosome 13 (del 13q) is the most common abnormality, being seen in around 50% of patients. It is associated with a good prognosis

Deletions of part of the short arm of chromosome 17 (del 17p) are seen in around 5-10% of patients and are associated with a poor prognosis

149

What is the presentation of chronic myeloid leukaemia?

Anaemia

Splenomegaly, often massive

Weight loss

Hyperleukostasis - fundal haemorrhage and venous congestion, altered consciousness, respiratory failure. Also known as tumour lysis syndrome

 

Gout from a high cell turnover

150

What mediates chronic tissue rejection?

Other innate components

Cytokines and antibodies cause myointimal proliferation in the arteries - blocks blood vessels and leads to ischaemia and fibrosis

151

What is platelet count in ET?

Greater than 600 x 10^9

152

What is the presentation of neutropenic sepsis?

Fever with no localising signs

Single reading of >38.50C or 380C on two readings one hour apart

Rigors

Chest infection/ pneumonia

Skin sepsis - cellulitis

Urinary tract infection

Septic shock

153

What mutation is assocaited with polycythaemia vera

JAK2V617F in 95%

154

Fresh frozen plasma table

155

What is the disease mechanism of chronic myeloid leukaemia?

Neoplastic monoclonal proliferation of ature granulocytes/precursors

 

Mature granulocytes accumulate in the bone marrow causing physical suppression which prevents maturation


Chronic myeloid leukaemia is assocaited with the philidelphia chromosome - t(9,22) BCR-ABL1 fusion - chimeric protein with strong tyrosine kinase activity (in over 90% of individuals)

156

What is the presentation of 22q11 deletion syndrome?

CATCH 22

Cardiac abnormalities

Abnormal facies

Thymic hypoplasia

Cleft palate

Hypocalcaemia

 

Also includes:

- Learning difficulties

157

What type of anaemia does beta thalassaemia cause?

Microcytic

158

What causes non-hodgkin lymphoma?

B/T cell tumours

No Reed-sternberg cells

159

What is the most common presentation for haemophilia?

Most presentation is between 6 months and 2 years. The baby starts walking and then all of a sudden stops walking, because they have had a bleed in their joint and don’t want to walk on it. Don’t jump to non accidental injury until you rule out bleeding disorder.

160

What antibodies does the person have if they have AB type blood?

No antibodies

161

What is myeloma a cancer of?

Bone marrow plasma cells

162

What is the essential test to do if there is a normocytic anaemia?

Want to perform a reticulocyte count and establish if the bone marrow is working correctly

163

What is the immunological presentation of 22q11 syndrome?

Recurrent RTI's during infancy

Low T cell numbers

Low IgA and IgM

Reduced antibody response

 

Autoimmune phenomena:

-Anaemia/thrombocytopenia

Juvenile chronic arthritis (JIA)
Raynauds

Thyroid disease

164

What is the presentation of chronic lymphocytic leukaemia?

Most common leukaemia in adults

Agent Orange exposure

 

- Anaemia (SOB, fatigue, pallor)

- Thrombocytopenia (bruising, petechiae, epistaxis)

- Neutropenia (bacterial infections, pneumonia, sepsis)

 

Neoplastc infiltration:

- Bone marrow (bone pain)

- Thymus (palpable mass/airway compression)

- Liver and spleen (hepatosplenomegaly)

- Lymphadenopathy

- Headaches, vomitting, nerve palsies, nuchal rigidity

165

How is the diagnosis of haemophilia made?

Prolonged APTT (activated partial thromboplastin time)
Normal PT (prothrombin time)

166

What is the supply of blood in someone who has received a massive haemorrhage?

6 units of red cells

4 units of fresh frozen plasma

1 units of platelets

167

What are indicators for treatment for chronic lymphocytic leukaemia?

Progressive bone marrow failure

Massive lymphadenopathy 

Progressive splenomegaly

Lymphocyte doubling time <6 months or >50% increase over 2 months

Systemic symptoms

Autoimmune cytopenias

168

Drugs for DVT

Drugs for DVT:

Anticoagulants:

LMWH

Warfarin

DOACs

 

Thrombolysis only in selected cases:

Massive PE

E.g streptokinase, tissue plasminogen activator

169

What causes alloantibodies?

Transfusion reactions

170

How do cellular immnodeficiencies arise?

Impaired T cell function or the absence of normal T cells

171

What is the treatment of acute myeloblastic leukaemia?

Anti-leukaemic chemotherapy (to achieve consolidation and remission)

Danorubicin

Cytosine arabinoside

Gemtuzumab  

Ozgamicin

CPX351

All trans retinoic acid and arsenic trioxide in low risk acute promyelocytic leukaemia (chemo free) high cure rate - 90%

 

Targeted Treatment:

Midostaurin in FLT3 mutated AML

 

Targeted antibodies:

Gemtuzumab Ozogamicin anti-CD33 with Calicheomycin (Mylotarg) - (think of Milo playing tig) 

Targeted small molecules

Midostaurin, Tyrosine Kinase Inhibitor including inhibiting FLT3

New delivery systems

CPX -351 - old fashioned chemotherapy but in a lipid molecule

 

 

172

What is the difference between a venous and an arterial clot?

Arterial thrombus = white clot - platelets and fibrin, results in ischaemia and infarction, principally secondary to atherosclerosis.

 

‘Red thrombus’~fibrin and red cells

Results in back pressure

Principally due to stasis and hypercoagulability

173

What are investigations for lymphoma?

IgM paraproteins

Biopsy (lymph node, bone marrow)

CT scan

Bone marrow aspirate and trephine

174

What are the symptoms of acute lymphoblastic leukaemia?

2-3 week history of bone marrow failure or bone/joint pain.

 

Anaemia

Tiredness

Fatigue

Infection

Bone marrow can necrose because it is full of rapidly dividing cells

Bone pain

Limp or hip pain (red flag symptom in children)

 

Osmosis:

- Anaemia (SOB, fatigue, pallor)

- Thrombocytopenia (bruising, petechiae, epistaxis)

- Neutropenia (bacterial infections, pneumonia, sepsis)

 

Neoplastc infiltration:

- Bone marrow (bone pain)

- Thymus (palpable mass/airway compression)

- Liver and spleen (hepatosplenomegaly)

- Lymphadenopathy

- Headaches, vomitting, nerve palsies, nuchal rigidity

175

What is virchows triad?

Stasis

Hypercoagubility

Vessel damage

 

Stasis = bed rest, travel

Hypercoagulability = pregnancy, trauma

Vessel damage = atherosclerosis

176

What is a potential treatment for SCID?

HSCT - haematopoeitic stem cell transplantation

177

How is non-hodgkin lymphma classified?

B cell or T cell lineage

Grade of disease (high grade or low grade)

Histological features of the disease

178

What is the treatment for FNHTR and urticaria following blood transfusion?

FNHTR = anti-pyretics

Urticaria = Antihistamines

179

How do you distinguish TACO from TRALI?

TACO is frequently confused with TRALI as a key feature of both is pulmonary oedema and it is possible for these complications to occur concurrently. Hypertension is a constant feature in TACO whereas it is infrequent and transient in TRALI.

180

What are the signs and symptoms of thrombocytopenia?

•Petechia (Venous pressure is higher in the leg than anywhere else – more likely to have petechiae)

•Ecchymosis (discolouration of the skin resulting from bleeding underneath, typically caused by bruising)

•Mucosal Bleeding

•Rare CNS bleeding

181

What is necessary for the diagnosis of acute myeloid leukaemia?

Blast cell count has to be greater than 20% for the diagnosis

 

Less than 20% may indicate myelodysplastic syndrome

182

What is seen on blood film of G6PD deficiency?

Hein Bodies

183

How does SCID present?

Recurrent infections

Diarrhoea, malabsorption and failure to thrive

Oral candidiasis with prominent thrush

 

Complications in clude susceptibility to severe infections such as:

andida albicans, pseudomonas, pneumocystiss jiroveci, cytomegalovirus, varicella

184

What mutation is assocaited with essential thrombocytopenia?

JAK2 mutation in around 50% of patients

Can also be associated with the CALR mutation in around 25% of individuals

185

What are the causes of thrombocytopenia?

Decreased production:

Marrow failure

Aplasia

Infiltration

 

Increased consumption

Immune ITP

Non immune DIC (caused by septicaemia, malignancy and eclampsia)

Hypersplenism

186

What is the managment of TACO?

Stop transfusion immediately and follow other steps for managing suspected transfusion reactions.

Place the patient in an upright position and treat symptoms with oxygen, diuretics and other cardiac failure therapy.

187

How do we figure out if haemolysis is immune or non-immune?

DAT test will tell you wether or not it is immune or non-immune. DAT positive = immune, DAT negative = not immune. Of the immune reactions the positive types can be further subdivided into warm-autoantibody, cold antibody and allo antibody.

188

What are complications in therapy for haemophilia?

Viral infection: HIV, HBV, HCV

Development of inhibatory antibodies for factor 8 (up to 10-15% of patients with haemophilia A)

DDAVP SE include MI and hyponatraemia