Haematology

Question 1

The main component involved in stabilising the primary haemostatic plug.

Answer 1

Fibrin

Question 2

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

Answer 2

Tissue plasminogen-activator (t-PA)

Question 3

A potent inhibitor of plasmin in the blood.

Answer 3

a2 macroglobulin

Alpha 2 macroglobulin acts as an antiprotease and is able to inactivate an enormous variety of proteinases. It functions as an inhibitor of fibrinolysis by inhibiting plasmin and kallikrein. It functions as an inhibitor of coagulation by inhibiting thrombin.

Question 4

A single chain glycoprotein, synthesised by the liver and endothelium, which has strongly anticoagulant action and is important in the mode of action of heparin.

Answer 4

Antithrombin III

Question 5

It is an important enzyme present in blood that degrades many blood plasma proteins, including fibrin clots.

Answer 5

plasmin

Question 6

This product of the cyclic endoperoxides induces platelet aggregation

Answer 6

Thromboxane A2

Question 7

A 6 foot 7 inch rower presents to his GP complaining of easy skin bruising. On further examination he is found to have pectus excavatum, lax joints and a high-arched palate.

Answer 7

Ehlers-Danlos syndrome

Question 8

A 62 year old overweight woman presents to the Emergency Department following a Road Traffic Accident. A full set of investigations is carried out – which shows an increased Activated Partial Thromboplastin Time (APTT) and Prothrombin Time (PT)/INR

Answer 8

vitamin K deficiency

Question 9

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.

Answer 9

von Willebrand deficiency

↓ platelet function and ↓ factor VIII (vWF carries factor VIII in circulation)

o Mostly autosomal dominant affecting 1/10,000 o Presentation: often bleeding indicative of platelet disorders (i.e. mucocutaneous bleeding) but can also include bleeding indicative of coagulation disorders

o Diagnosis:↑APTT, ↑bleedingtime

↓FactorVIII,↓vWFAg. NormalINR&plts o Management:Desmopressin,VWFandFactorVIIIconcentrates

Question 10

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.

Answer 10

• ATP
• Glycoprotein IIb/IIIa on platelets
• Anti Platelet Antibody Steroids
• IVIG
• Anti-D Antibody,

Question 11

Factor VIII deficency

Answer 11

Hemophila A X-linked recessive affecting 1/10,000 males

o Presentation: often early in life or prolonged bleeding after surgery/trauma

o Diagnosis: ↑APTT, normal PT and ↓ factor VIII assay.

oManagement:AvoidNSAIDsandI

Minjections,desmopressin(􏰉vWFrelease which is VIII carrier), factor VIII concentrates as replacement which is life long

Question 12

Factor IX

Answer 12

Chrismas Diseases X-linked recessive affecting 1/10,000 males o Presentation: often early in life or prolonged bleeding after surgery/trauma o Diagnosis: ↑APTT, normal PT and ↓ factor IX assay. o Severity:relatedtofactorleveleg.sev<1%,mod1-5%,mild5-25% o Management:AvoidNSAIDsandIMinjections,desmopressin(􏰉vWFrelease which is VIII carrier), factor VIII concentrates as replacement which is life long

Question 13

It inhibits platelet activation and is also an effective vasodilator.

Answer 13

Prostacylin

Question 14

Which protein, important in haemostasis, is vitamin K dependent but is not a serine protease? Which option is required as a cofactor for protein C activity?

What does it do?

Answer 14

Protein S

Inhibits factor Va and XIII

Question 15

Which option synthesises TF, vWF, prostacyclin, plasminogen activator, antithrombin III and thrombomodulin?

Answer 15

Vascular endothelium

Question 16

Which enzyme, important for platelet aggregation, is irreversibly inhibited by aspirin?

Answer 16

Cyclooxygenase

Question 17

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

Answer 17

Thrombin

Question 18

can reversibly inhibit Factor Xa

While Xa is inhibited, the Xa- “ XXXX’’ complex can subsequently also inhibit the FVIIa-TF complex.

Answer 18

Tissue factor pathway inhibitor (or TFPI) is a single-chain polypeptide which can reversibly inhibit Factor Xa (Xa). While Xa is inhibited, the Xa-TFPI complex can subsequently also inhibit the FVIIa-tissue factor complex.

Question 19

It connects intrisinc and extrinsinc pathway

Answer 19

Factor X

Question 20

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

Answer 20

vitamin K deficiency

- increased PT/INR = vitamin K

Question 21

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

Answer 21

vWF 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

Question 22

A 32 week pregnant lady who has gestational diabetes and is epileptic has a caesarean section while on holiday in rural China. Her newborn baby is suffering from bleeding from the umbilical stump, as well as nose and gums. What is wrong with the baby?

Answer 22

vitamin K deficiency- babies in the UK are given vitamin K post-birth

Question 23

IgA mediated vasculitis In children < 10 years Preceding URTI Palpable purpuric rash (lower libs extensors + buttocks) Colicky abdo pain Glomerulonephritis Arthritis Orchitis

Answer 23

HSP

Question 24

Skull bossing, maxillary hypertrophy, hairs on end skull X-ray, 􏰂 Hepatosplenomegaly

Answer 24

β Thalassaemia:

o β- thalassaemia major (homozygous) → 3-6mths severe anaemia, FTT, hepatosplenomegaly (extramedullary erythropoiesis), bony deformity, severe anaemia + heart failure

Diagnosis: Hb electrophoresis (Guthrie at birth) Treatment: blood transfusions and desferrioxamine to stop iron overload, plus folic acid

􏰂 Point mutations – ↓ β-chain synthesis (spectrum of disease), excess α-chains 􏰂 ↑HbA2 and HbF

o β- thalassaemia minor (heterozygous) → Asymptomatic carrier, mild anaemia

Question 25

Features mild hypochromic, microcytic anaemia - microcytosis is characteristically disproportionate** to the anaemia **HbA2 raised (> 3.5%)

Answer 25

β Thalassaemia minor

Question 26

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.

Answer 26

A rare autosomal dominant disorder. Alternative name = HHT

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

Question 27

A fit 48-year-old investment banker presents to A&E with a painful R arm that was present when he woke up that morning. He is otherwise well and there is no history of trauma or abnormalities of any system. On examination there is marked tenderness and mild erythema along the anterolateral aspect of the forearm and cubital fossa, with no abnormality of the upper arm or axilla.

Answer 27

Superficial venous thrombosis

Question 28

A 45-year-old lady, known heavy smoker with chronic respiratory problems, presents to her GP with increasing dyspnoea and swelling of her R arm and face.

On examination of her chest there is no asymmetry or tracheal deviation, but there are added sounds over the R upper lobe and on bending forward her face becomes congested.

Answer 28

Superior vena caval obstruction

Question 29

A 56-year-old woman returns to the Vascular Clinic with recurrence of her L leg ulcer after the area has been knocked by a shopping trolley.

On examination the ulcer is situated above the medial malleolus, its dimensions being 6cm x 5cm. The base is filled with yellowish slough and the surrounding area is erythematous, with prominent oedema.

Answer 29

Postphlebitic syndrome

Post-thrombotic syndrome (PTS), also called postphlebitic syndrome and venous stress disorder is a medical condition that may occur as a long-term complication of deep vein thrombosis (DVT).

Question 30

A 48-year-old man develops R-sided pleuritic chest pain and coughs-up a trace of bloodstained sputum 8 days after a R hemicolectomy.

He has mild dyspnoea but chest examination and chest radiography are normal.

Answer 30

Pulmonary embolism

Question 31

A 32-year-old lady develops acute swelling of her L leg 2 days post-partum. She had bilateral leg swelling during the pregnancy but the delivery was normal. On examination there is tense swelling of the leg and thigh and some deep tenderness over the calf and medial aspect of the thigh.

Answer 31

DVT

Question 32

Trousseau’s syndrome (25%)- recurrent superficial thrombophlebitis is associated with which pathology?

Answer 32

pancreatic cancer

Question 33

Patients presenting with malignancy, sepsis, trauma, obstetric complications, toxins.

Low plts, low fibrinogen, high FDP/ddimer, long PT/INR

(low platelets - high evrything else)

Answer 33

Acquired: Disseminated intravascular coagulation (DIC):

o Widespreadactivationofcoagulation

o Clotting factors and platelets are consumed → ↑ risk of bleeding

o Treat the cause and give transfusions, FFP, platelets, cryo etc

Question 34

A drug that is administered intravenously and has a rapid effect by potentiating the action of antithrombin. Action can be reversed quickly which is of relevance in myocardial infarction patients who may require early invasive treatment (ie PTCA).

Answer 34

Unfractionated heparin (UFH)

Question 35

Potentiates antithrombin III. Usually given subcutaneously. Can cause osteoporosis and hyperkalaemia.

Answer 35

Dalteparin (LMWH)

Question 36

Used to monitor patients undergoing warfarin therapy.

Answer 36

PT, monitor wafarin therpahy, starts with factor VII

Question 37

Used to monitor patients undergoing unfractionated heparin therapy.

Answer 37

APTT, used to monitor heparin theraphy. Starts with factor XII

Question 38

This anticoagulant drug is directly contraindicated in pregnancy, especially the first 16 and last 4 weeks of a 40 week gestation.

Answer 38

Warfarin

Warfarin is an oral anticoagulant which inhibits the reduction of vitamin K to its active hydroquinone form, which in turn acts as a cofactor in the carboxylation of clotting factor II, VII, IX and X (mnemonic = 1972) and protein C!!!!!!

teratogenic, although can be used in breast-feeding mothers

Question 39

Reflects the amount and activity of fibrinogen.

Answer 39

Thrombin time (TT) as Thrombin converts Fibrnogen to Fibrin

Question 40

Antiplatelet action. Indicated for primary prophylaxis of stroke in a patient experiencing recurrent retinal TIAs (amaurosis fugax). Ineffective for DVT prophylaxis.

Answer 40

Aspirin

Aspirin works by blocking the action of both cyclooxygenase-1 and 2. Cyclooxygenase is responsible for prostaglandin, prostacyclin and thromboxane synthesis.

Question 41

Antiplatelet action. Licensed for secondary prophylaxis of stroke. More effective than aspirin alone.

Answer 41

Dipyridamole modified release (MR) and aspirin

Dipyridamole

Dipyridamole is an antiplatelet mainly used in combination with aspirin after an ischaemic stroke or TIA

Mechanism of action

inhibits phosphodiesterase, elevating platelet cAMP levels which in turn reduce intracellular calcium levels

other actions include reducing cellular uptake of adenosine and inhibition of thromboxane synthase

Question 42

Antiplatelet action. clopidogrel is also now first-line in patients following an ischaemic stroke and in patients with peripheral arterial disease.

Answer 42

Clopidogrel antagonist of the P2Y12 adenosine diphosphate (ADP) receptor, inhibiting the activation of platelets

Question 43

Dangerous combination with no added efficacy and increased GI bleed.

Answer 43

Clopidogrel and aspirin

Question 44

Old model of starting warfarin

Answer 44

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

Question 45

New (recommended, Tait) model of starting warfarin

Answer 45

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

Question 46

In patients with metallic heart valves, this drug is the most effective anticoagulant

Answer 46

Warfarin

Question 47

In patients with cancer and acute venous thromboembolism, the most effective drug at reducing the risk of recurrent VTE is __?

Answer 47

Dalteparin (LMWH)

Question 48

This drug when given alone initially increases the clotting risk

Answer 48

Warfarin

Question 49

Side effects include cutaneous necrosis

Answer 49

Warfarin

Question 50

The drug most likely to cause thrombocytopaenia with paradoxical thrombosis - remember HIT the Wafarin!!!

Answer 50

Unfractionated heparin (UFH)

SE:

Bleeding
Heparin-induced thrombocytopaenia (HIT)
Osteoporosis

Question 51

Indicated as thrombotic prophylaxis in DIC

Answer 51

Dalteparin (LMWH)

Question 52

Contra-indicated if recent sore throat, if ever used before, or in the presence of proliferative retinopathy.

Answer 52

Streptokinase

Question 53

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.

Answer 53

Chronic Myelomonocytic Anaemia

Question 54

An alcoholic presents to your clinic with anaemia. Sideroblasts are observed on morphological examination.

What is it caused by??

Answer 54

Secondary Sideroblastic Anaemia

Ineffective erythropoiesis → iron loading (bone marrow) causing haemosiderosis
(endocrine, liver and cardiac damage due to iron deposition)
Diagnosis: Ring sideroblasts seen in the marrow (erythroid precursors with iron
deposited in mitochondria in a ring around the nucleus).
Causes: myelodysplastic disorders, following chemotherapy, irradiation, alcohol
excess, lead excess, anti-TB drugs or myeloproliferative disease.
Treatment: Remove the cause and Pyridoxine (vitamin B6 promotes RBC production).

Question 55

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.

Answer 55

Refractory Cytopaenia with Multilineage Dysplasia

1) Why? this patient is tired, easy bruisng, fatique.
2) Bone marrow aspirate indicates dysplasia in different linages of the blood

Question 56

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.

Answer 56

Again, this patien is eldery, presents with reccurent infections and excess blast.

Refractory Anaemia with excess of Blasts II

Question 57

You are called to A&E to see a 65 year old man. He is complaining of fever, shortness of breath, and has lost 5Kg in the last few months. His notes say he was previously diagnosed with “Refractory Anaemia with excess Blasts in Transformation” (RAEB-t). His blast cell count is approximately 30% of all nucleated cells.

Answer 57

Acute Myeloid Leukaemia

Question 58

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

Answer 58

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

Question 59

A 34 year old man with peripheral cytopenia suffers from bleeding gums. Peripheral blood shows 5% blast cells and bone marrow 42% blast cells.

Answer 59

Acute Myeloid Leukaemia

As listed above, plus:
Lymphadenopathy less common
Quick subtype facts:
M3: Acute promyelocytic
leukaemia – prone to DIC
M4+5: Monoblasts/monocytes -
Skin / gum infiltration +
hypokalaemia

High WCC
Auer rods and granules
Myeloperoxidase and Sudan black
B stains

Question 60

A 20 year old man with hepatitis C complains of fatigue and breathlessness and bruises very easily.

Answer 60

secondary aplastic anemia

why?

Fatigue-breathlessnes and easy brusing are common indication of the bone marrow problem.

Fatigue (RBC) and platlets (low)- brusing.

This patinet also has Hep C, which causes the aplastic anemia

Question 61

This patients blood film shows classic Pelger-Huet neutrophils and bone marrow blasts make up 15% of cells.

Answer 61

Refractory anaemia with an excess of blasts

Question 62

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

Answer 62

Refractory cytopenia with multilineage dysplasia

Question 63

A 64 year old man complains of headaches, fatigue and itchy skin, particularly evident after a hot bath. He has a long-standing history of alcohol abuse and drug history reveals that he taking thiazide diuretics. On examination, you note that he is thin with sunken eyes.

Answer 63

Pseudopolycythaemia- dehydration

Question 64

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.

Answer 64

Essential thrombocythaemia

is a rare chronic blood disorder characterised by the overproduction of platelets by megakaryocytes in the bone marrow. It may, albeit rarely, develop into acute myeloid leukaemia or myelofibrosis.

Question 65

A 53 year old man goes to see his doctor about an embarrassing problem. It seems that his friends have nicknamed him ‘Rudolph’. You seem quite confused, but all becomes apparent when he points to his nose, which appears red. After further questioning, he describes a ‘burning’ sensation on his nose, hands and feet and visual disturbances. You send him for ‘blood tests’. What do you expect to be raised?

Answer 65

Haematocrit

Question 66

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?

Answer 66

Imitanib

Chronic Myeloid Leukaemia

Ph+ve (Philadelphia chromosome) in 80% = chromosomal translocation (9;22)
􀁸 PCR for BCR-ABL (Philadelphia Ch) fusion gene

BCR-ABL tyrosine kinase inhibitor
􀁸 Monitor disease and therapeutic response
􀁸 WBC, Neutrophils 50-500
􀁸 Hypercellular BM with spectrum of immature (e.g. myelocytes) and mature
granulocytic cells in the blood

Question 67

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?

Answer 67

Tear drop poikilocytes:

A dacrocyte (or dacryocyte) is a type of poikilocyte that is shaped like a teardrop (a“teardrop cell”). A marked increase of dacrocytes is known as “dacrocytosis”. These tear drop cells are found also in beta thalassemia major, especially after splenectomy.

Question 68

erythromelalgia

Answer 68

Burning sensation of the hands and feet is denoted by the term

Question 69

A 64-year old woman receiving long-term chemotherapy for lymphoma presents with worsening bone pain, recurrent fever and night sweats. Blood film shows blast cells with Auer Rods.

Answer 69

Acute myeloid leukaemia

As listed above, plus:
Lymphadenopathy less common

Quick subtype facts:
M3:Acute promyelocytic leukaemia – prone to DIC
M4+5: Monoblasts/monocytes - Skin / gum infiltration + hypokalaemia

High WCC
Auer rods and granules
Myeloperoxidase and Sudan black B stains

High WCC

Chemotherapy:
Similar principles to ALL but…
No CNS prophylaxis / maintenance
therapy needed
Consider allo-SCT in young

Specific: ATRA for M3 (acute promyelocytic leukaemia)
Supportive:
Similar principles to ALL
Prognosis worse with age

Question 70

A 61-year-old man with CLL presents with recurrent pneumonia and haemoptysis. On fibreoptic bronchoscopy, the patient is found to have an endobronchial mass. The biopsy shows anaplastic, large cell lymphoma.

Answer 70

Richter’s syndrome is a tranformation of CLL to diffuse large B-cell lymphoma

Chronic lymphocytic leukaemia (CLL) is caused by a monoclonal proliferation of well-differentiated lymphocytes which are almost always B-cells (99%)

Features

often none

constitutional: anorexia, weight loss

bleeding, infections

lymphadenopathy more marked than CML

Symmetrical painless lymphadenopathy

Complications

hypogammaglobulinaemia leading to recurrent infections

warm autoimmune haemolytic anaemia in 10-15% of patients

transformation to high-grade lymphoma (Richter’s transformation)

Investigations

blood film: smudge cells (also known as smear cells)

immunophenotyping

Prognostic factors
􀁸 LDH raised, CD38 +ve, 11q23 deletion = bad
􀁸 Hypermutated Ig gene, Low ZAP-70 expression, 13q14 deletion = good

Question 71

A newly diagnosed ALL patient complains of tiredness, polyuria, polydipsia, abdominal pain and vomiting on receiving chemotherapy. On examination, BP: 160/100mmHg, temp: 39ºC, and ECG shows tented T waves. Blood test shows serum K+: 6.9mmol/L and phosphate: 7.1 mmol/L. (hypokalemia getting out of control - potassium goes outside the cells)The patient later dies of cardiac arrest.

Answer 71

Tumour-lysis syndrome

Tumour lysis syndrome (TLS) is a potentially deadly condition related to the treatment of high grade lymphomas and leukaemias.

It can occur in the absence of chemotherapy but is usually triggered by the introduction of combination chemotherapy.

On occasion it can occur with steroid treatment alone.

Question 72

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.

Answer 72

Chronic myeloid leukaemia:

A myeloproliferative disease
Middle-aged (40 to 60); median survival 3-5 years.
Often diagnosed on routine bloods (large number of differentiated neutrophils), now very
successfully treated in the majority
O/E: splenomegaly - often massive
Investigations:
􀁸 Ph+ve (Philadelphia chromosome) in 80% = chromosomal translocation (9;22)
􀁸 PCR for BCR-ABL (Philadelphia Ch) fusion gene
􀁸 Monitor disease and therapeutic response
􀁸 WBC, Neutrophils 50-500
􀁸 Hypercellular BM with spectrum

Question 73

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

Answer 73

Acute lymphoblastic leukaemia

All clinical features listed above, plus:
Lymphadenopathy +++
CNS involvement +++
Testicular enlargement
Thymic enlargement (mediastinum)

Maintenance: 2 years in girls and adults, 3 years in boys:
Consider allo-Stem Cell Transplant
Supportive: Blood products, ABx,
Allopurinol, fluid, electrolytes – to
prevent tumour lysis syndrome

Question 74

A patient has acute lymphoblastic leukaemia. A bone marrow biopsy will show infiltration by which cells?

Answer 74

Blast cells (lymphocyte precursors)

Question 75

Patients with this inherited disorder have an increased risk of developing acute leukaemia.

Answer 75

Down’s syndrome

Question 76

An environmental factor associated with acute leukaemia.

Answer 76

Ionising radiation

Question 77

A 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?

Answer 77

Neutrophils CML. Increased mass of turning-over cells generates urate.

Investigations:
􀁸 Ph+ve (Philadelphia chromosome) in 80% = chromosomal translocation (9;22)

Question 78

A 65yr old lady is seen in the haematology clinic where she has been treated for 7 years with Imantinib for CML. Having been previously well, she is now complaining of shortness of breath and general weakness. Examination reveals splenomegally. Her peripheral blood film has changed from previous appointments and reflects the progression of her disease. Which type of cell is now proliferating?

Answer 78

Blast cells CML, blast phase. Transformation tends to be into AML but in 20% is lymphoblastic (ALL). Splenomegaly is characterisitic feature

Blast Phase
􀁸 >20% blasts in BM/blood
􀁸 Resembles ALL; timeframe = months (+/- WL, lethargy, night sweats)
􀁸 Treatment similar to AML, possibly with allogeneic SCT for young pts.

Chronic phase
􀁸 <5% blasts in BM/blood, WBC slowly increases over years (indolent)
􀁸 Rx = Oral hydroxyurea/interferon suppress WCC. Imatinib (BCR-ABL tyrosine kinase
inhibitor) or dasatinib/nilotinib for resistance; extremely effective. BMT potentially
curative.
Accelerated Phase
􀁸 >10% blasts in BM/blood
􀁸 Increasing manifestations, such as splenomegaly, lasting up to a year
􀁸 Less responsive to therapy

Question 79

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?

Answer 79

Clonal B lymphocytes 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.

Question 80

A routine full blood count on a 62yr old gardener reveals a high white cell count of 154x109 /L, and the differential shows this to be a neutrophilia. The haemoglobin and platelet count are normal. Biopsy shows a hypercellular “packed” bone marrow, and cells show the presence of which chromosomal abnormality?

Answer 80

Chromosome 9;22 translocation

Question 81

Moderate anaemia, splenomegaly, bony deformity, gallstones

Answer 81

o β- thalassaemia intermedia

Question 82

Skin pigmentation, nail dystrophy, oral leukoplakia (triad) + BM failure

Answer 82

Dyskeratosis Congenita

􏰂 X-linked. Chromosome instability (telomere shortening)

Question 83

A 60 year old female patient with the following blood results: neutrophils 0.4 x 109/l, platelets 19 x 109/l and reticulocytes 50 x109/l.

Answer 83

The inability of BM to produce adequate blood cells

􏰂 Haemopoeitic stem cell numbers are reduced in BM trephines (hypocellular BM)=but there are no blasts, if the blasts were present this would mean it is refractory anemia with excess/low number of blasts.

􏰂 AA typically refers to anaemia – i.e. just RBCs – however these patients can have a

pancytopenia as well

􏰂 Symptoms/signs relate to each cytopaenia

􏰂 Patients typically present with bleeding problems

􏰂 Can affect any age

Question 84

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.

Answer 84

AML

Auer Rods

Blast cells (20%)

Quick subtype facts:
M3: Acute promyelocytic leukaemia – prone to DIC

Specific: ATRA for M3 (acute promyelocytic leukaemia)

M4+5: Monoblasts/monocytes - Skin / gum infiltration + hypokalaemia

Question 85

An 83 year old woman presents to the A&E Departments with severe weakness and SOB (pancytopenia)

On examination, masses are felt in both left and right upper quadrants of the abdomen (hepato and splenomegaly) Blood film show leukoerythroblastic cells and teardrop poikilocytes.

Answer 85

A MPD where myeloproliferation􏰀fibrosis of BM or replacement with collagenous tissue 􏰂

Primary (idiopathic) vs secondary following PRV, ET, leukaemia etc).

􏰂 Usually elderly

􏰂 Pancytopaenia-related symptoms

􏰂Extramedullary haematopoeisis - hepatomegaly, massive splenomegaly, WL, fever

Investigations

􏰂Blood film – tear-drop poikilocytes (dacrocyte), leukoerythroblasts (primitive cells)

􏰂 BM – fibrosis, “dry tap”

Treatment

􏰂 Support with blood products, in some cases - splenectomy

􏰂 Hydroxycarbamide, thalidomide, steroids and SCT also used.

Question 86

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

􏰂

Answer 86

Fanconi anaemia

Inherited AA / BM failure syndrome

Fanconi Anaemia (cf Fanconi Syndrome = renal)

􏰂 Autosomal recessive. Pancytopenia

􏰂 Presents at 5-10yrs

Question 87

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

Answer 87

Paroxysmal nocturnal haemoglobinuria:

􏰂 Acquired loss of protective surface GPI markers on RBCs (platelets + neutrophils) → complement-mediated lysis → chronic intravascular haemolysis especially at night.

􏰂 Morning haemoglobinuria, thrombosis (+Budd- Chiari syndrome – hepatic v thromb).

􏰂 Diagnosis: immunophenotype shows altered GPI or Ham’s test (in vitro acid-inducedlysis).

􏰂 Treatment: iron/folate supplements, prophylactic vaccines/antibiotics. Expensive

monoclonal antibodies (eculizumab) that prevents complement from binding RBCs

Features

haemolytic anaemia

red blood cells, white blood cells, platelets or stem cells may be affected therefore pancytopaenia may be present

haemoglobinuria: classically dark-coloured urine in the morning (although has been shown to occur throughout the day)

thrombosis e.g. Budd-Chiari syndrome

aplastic anaemia may develop in some patients

Diagnosis

flow cytometry of blood to detect low levels of CD59 and CD55 has now replaced Ham’s test as the gold standard investigation in PNH

Ham’s test: acid-induced haemolysis (normal red cells would not)

Management

blood product replacement

anticoagulation

eculizumab, a monoclonal antibody directed against terminal protein C5, is currently being trialled and is showing promise in reducing intravascular haemolysis

stem cell transplantation

Question 88

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

Answer 88

Gaucher’s disease (glucosylceramide lipidosis)

Massive splenomegaly

myelofibrosis

chronic myeloid leukaemia

visceral leishmaniasis (kala-azar)

malaria

Gaucher’s syndrome

Question 89

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.

Question 90

generally seen in young children and produces a triad of:

acute renal failure

microangiopathic haemolytic anaemia

thrombocytopenia

Answer 90

HUS: Haemolytic uraemic syndrome.

toxin damages endothelial cells􏰀fibrin mesh and RBC damage􏰀impaired renal function + microangiopathic haemolytic anaemia.

Diarrhoea, renal failure, no neuro problems, children and elderly.

Question 91

• failure to thrive
• jaundice, gallstones
• splenomegaly
• aplastic crisis precipitated by parvovirus infection
• degree of haemolysis variable
• MCHC elevated

Answer 91

Hereditary spherocytosis

Question 92

Clinical features: can be severe neonatal jaundice, splenomegaly, haemolytic anaemia

􏰂 Treatment: most do not require treatment (can incl blood transfusion or splenectomy)

Answer 92

Pyruvate kinase deficiency

􏰂 Autosomal recessive (but autosomal dominant has been observed with the disorder)

Question 93

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?

Answer 93

G6PD - dapsone

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.

Question 94

In which condition might a Donath-Landsteiner be positive?

Answer 94

Paroxysmal cold haemoglobinuria

Cold Agglutinin Disease

Features

>37oC

IgM

Positive Coombs test

Often with Raynaud’s

Causes

Lymphoma, Infections: EBV, mycoplasma

Management

Steroids

Treat underlying condition

Splenectomy

Avoid the cold

Immunosuppression

Chlorambucil (chemo)

Question 95

A 49 year old female complains of abdominal pain and vomiting a few minutes after the start of transfusion. O.E she is tachycardic and has facial flushing. Urinalysis reveals haemoglobinuria.

Answer 95

Immediate Transfusion Reaction

ABO incompatbility

Question 96

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.

Answer 96

Febrile non-hemolytic transfusion reaction

Question 97

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.

Answer 97

Bacterial Infection of Unit

Question 98

A 78 year old man is found collapsed in his bathroom at home. Tests reveal that he is anaemic and has raised urea and creatinine levels. Over the next 24 hours he receives 3 litres of fluid and a blood transfusion. He then becomes dyspnoeic. Examination reveals a raised JVP, basal crepitations and ankle oedema.

Answer 98

Fluid overload

Question 99

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

Answer 99

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

Question 100

In contrast, delayed haemolytic transfusion reaction (DHTR) manifests days to weeks after a transfusion, acommpanied by a falling haemoglobin and jaundice or haemoglobinuria.

Question 101

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.

Answer 101

Allergic reaction to transfusion

Question 102

A 36 year old Italian gentleman presented with severe bruising across the dorsal aspect of his left arm one week post-transfusion. FBC results included: Hb = 15g/dL, platelets = 8x109/L and WBC = 5.5x109/L.

Answer 102

Post Transfusion Purpura

Question 103

A 72 year old Australian man developed a fever and jaundice five days post-transfusion. FBC revealed Hb = 9g/dL and MCV = 105fL with haemoglobinuria noted on urine dipstick testing.

Answer 103

Delayed haemolytic transfusion reaction (DHTR)

Question 104

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

Answer 104

IgA deficiency

Question 106

Patient develops mild symptoms of fever and rigors a few days after transfusion, with a rise pulse rate.

Answer 106

febrile non-hemolytic transfusion reaction

Question 107

A 33 year old patient has just given birth to her second child. The baby is jaundiced and placed under a UV lamp. What investigation would you perform to test for foetal haemoglobin-containing red cells?

Answer 107

Kleihauer test

The Kleihauer–Betke (“KB”) test, Kleihauer–Betke (“KB”) stain, Kleihauer test or Acid elution test, is a blood testused to measure the amount of fetal hemoglobin transferred from a fetus to a mother’s bloodstream.

A Kleihauer test is used to confirm transplacental blood loss from fetus to mother. The test is performed on the mother’s blood; the blood undergoes acid elution and staining. Fetal red cells contain HbF and are therefore more resistant to acid elution than the maternal cells. The fetal cells therefore stain red, maternal cells stain pink.

Question 108

A 23 year old Middle Eastern man with beta thalassaemia major complains of a bronze skin discolouration.

Answer 108

Iatrogenic Iron overload

Question 109

A female infant presents to A&E with symptoms of hypoxia. It is noted that she has dactylitis.

Answer 109

sickle cell

Question 110

A child is known to have a blood disorder and seems to have suffered from a stroke. What is the blood disorder that this child is most likely to have?

Answer 110

Sickle Cell Disease

Question 111

A routine blood sample is taken from an asymptomatic neonate. Results reveal a raised Hb, a raised WCC and a raised MCV. Both Hb A and F are present.

Answer 111

Normal Neonate

Question 112

A male infant is admitted to hospital for a routine circumcision. During the operation haemostasis seems to be impaired. His mother failed to mention in the family history that her father had some sort of blood disorder.

Answer 112

Haemophilia, Factor VIII

X-linked recessive affecting 1/10,000 males
o Presentation: often early in life or prolonged bleeding after surgery/trauma
o Diagnosis: ↑APTT, normal PT and ↓ factor VIII assay.

!!!!!!!Rember this - it is very important!!!!!!!!
oSeverity:relatedtofactorleveleg.

Management:AvoidNSAID and Minjections,desmopressin(􏰉vWFrelease

which is VIII carrier), factor VIII concentrates as replacement which is life long

Question 113

A 6 month old girl is brought to her GP by her Greek Cypriot parents. They complain that she looks small compared to their neighbour’s baby of the same age. They also think her face looks funny. On examination, you note pallor and jaundice, the baby’s skull appears bossed and there is maxillary prominence. There is also marked hepatosplenomegaly. Her blood film shows a microcytosis and haemoglobin analysis shows high levels of HbF and HbA2.

Answer 113

Thalassaemia Major

Question 114

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.

Answer 114

Von Willebrand’s Disease

Von Willebrand’s disease

o Several types – quantitative (deficiency) vs. qualitative
o ↓ platelet function and ↓ factor VIII (vWF carries factor VIII in circulation)
o Mostly AD affecting 1/10,000 -Very Important!!!!
o Presentation: often bleeding indicative of platelet disorders (i.e. mucocutaneous bleeding) but can also include bleeding indicative of coagulation disorders
o Diagnosis:

↑APTT,↑bleedingtime,↓FactorVIII,↓vWFAg.

VWF) is the carrier molecule for FVIII, preventing its premature degredation in the circulation, so if VWF is low, FVIII is vulnerable to degredation and is therefore also low.

NormalINR&plts o Management:

Desmopressin, VWF and Factor VIII concentrates

Question 115

A baby with Down’s syndrome is noted, on routine blood testing, to have large numbers of circulating megakaryocyte blast cells and nucleated red blood cells. A repeat blood film 2 months later is normal.

Answer 115

Transient Abnormal Myelopoiesis

Question 116

What is the platlet count in Haemophila and vwD?

Answer 116

Haemophilia and VWD have normal platelet count.

Question 117

Why can G6PD levels be normal in G6PD deficiency? I

Answer 117

n an acute haemolytic crisis we would mount a reticulocyte response (young red cells) which have a high level of G6PD, therefore this may elevate the measured G6PD level. Therefore you would have to measure the G6PD level after the acute haemolytic episode has resolved, to see if the patient is truly G6PD deficient. ps polychromatic macrocytes = reticulocytes (polychromasia due to ribosomal RNA)

Question 118

You are asked to see a neonate who while being treated for a urinary tract infection with Nitrofurantoin has developed jaundice. The blood film shows Heinz bodies, “bite cells” and polychromasia. What is the likely diagnosis?

Answer 118

Glucose-6-phosphate dehydrogenase deficiency

Question 119

A 4 year old Afro-Caribbean girl presents to A&E with severe bony pain in her hands and feet and shortness of breath. Her oxygenation is 85% on air. On investigation her Hb is found to be very low at 6.3g/dl. What is the likely diagnosis?

Answer 119

B.

Sickle cell anaemia

Question 120

A 2 year old girl presents to his GP following a viral illness with purpuric rash, ecchymoses and epistaxis. Normal haemoglobin and white cell count and platelets 19x109/L. Bone marrow show increased numbers of megakaryocytes (platlets precursors(. What is the likely diagnosis?

Answer 120

Autoimmune thrombocytopenia

Thrombocytopenia (norm plt count 150- 400x109 g/l

Question 121

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?

Answer 121

Heampophila VIII (A)

Question 122

α- Thalassaemia:

􏰂Deletions - reduced α-chain synthesis, excess β-chains

􏰂 *4 α genes, severity depends on number deletedo α- thalassaemia trait (1/2 deleted) →

*HbH disease (3 deleted) →

*Hydrops Foetalis (4 deleted) →

Answer 122

• Asymptomatic, mild anaemia
• Moderate anaemia, splenomegaly
• Incompatible with life

Question 123

is a genetic disorder in which glucocerebroside accumulates in cells and certain organs.

The disorder is characterized by bruising, fatigue, anemia, low blood platelet count and enlargement of the liver and spleen, and is caused by a hereditary deficiency of the enzyme glucocerebrosidase (also known as glucosylceramidase), which acts on glucocerebroside. When the enzyme is defective, glucocerebroside accumulates, particularly in white blood cells and especially in macrophages (mononuclear leukocytes). Glucocerebroside can collect in the spleen, liver, kidneys, lungs, brain, and bone marrow.

Manifestations may include enlarged spleen and liver, liver malfunction, skeletal disorders or bone lesions that may be painful, severe neurological complications, swelling of lymph nodes and (occasionally) adjacent joints, distended abdomen, a brownish tint to the skin, anemia, low blood platelet count, and yellow fatty deposits on the white of the eye (sclera). Persons seriously affected may also be more susceptible to infection. Some forms of Gaucher’s disease may be treated with enzyme replacement therapy.

The disease is caused by a recessive mutation in the GBA gene located on chromosome 1 and affects both males and females.

Answer 123

Gaucher’s disease or Gaucher disease (/ɡoʊˈʃeɪ/) (GD)

About one in 100 people in the United States are carriers of the most common type of Gaucher disease. The carrier rate among Ashkenazi Jews

Question 124

Free light chains produced by abnormal plasma cells that are small enough to pass into the urine.

Answer 124

Bence jones protein

Question 125

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

Answer 125

amyloid

Question 126

A monoclonal immunoglobulin which appears as a dense narrow band (M band) on electrophoresis.

Answer 126

Paraprotein - IgG

Question 127

Stimulated by IL-6 secreted by cells in the vicinity of the myeloma cells. Produces radiological changes resembling those of generalized osteoporosis.

Answer 127

osteoclasts

Question 128

Misfolded protein deposited in myeloma-associated amyloidosis

Answer 128

Amyloidosis

Multisystem disorder caused by abnormal folding of proteins that are deposited as amyloid fibrils in tissues, disrupting their normal function.

Can be primary or secondary:

PRIMARY (AL amyloidosis)

● Most common

● Deposition of amyloid L protein

● Most associated with plasma cell dyscrasias and with paraproteins, e.g. multiple myeloma (although most don’t have multiple myeloma)

● Most have monoclonal Ig, f_ree light chains in serum_ and urine (Bence Jones) and increased bone marrow plasma cells

Question 129

A condition involving a low level of paraprotein (IgG secreted by the plasma cells) in the blood in usually asymptomatic elderly patients

Answer 129

MGUS: Monoclonal Gammaglobinopathy of Unknown Significance

• 􏰂 <10% plasma cells in marrow, <30g/l monoclonal paraprotein, no CRAB etc.
• 􏰂 Incidental finding; progresses to multiple myeloma at a rate of 1-2% / year
• “Smouldering Myeloma”: >10% plasma cells (+ >30g/l) in BM but no CRAB / organ/tissue involvement

Question 130

Induction chemotherapy regimen with the best evidence pre-autologous stem-cell transplant in multiple myeloma

Answer 130

Lenalidomide + low dose dexamethasone

Question 131

Monoclonal immunoglobulin raised in macroglobinaemia

Answer 131

Waldenstrom’s Macroglobinaemia (Lymphoplasmacytoid Lymphoma - LPL)

• 􏰂Elderly men
• 􏰂Weight loss, fatigue, hyperviscosity syndrome (visual problems, confusion, CCF, muscle weakness
• Lymphoplasmacytoid cells produce monoclonal serum IgM that
• infiltrates the LNs/BM

􏰂 Treatment: plasmapheresis for hyperviscosity; chlorambucil,

cyclophosphamide and other chemo

Question 132

Factor(s) associated with a very poor prognosis in multiple myeloma

Answer 132

Anaemia & renal failure

Question 133

Proteasome inhibitor active in myeloma

Answer 133

Bortezomib

Question 134

Asymptomatic, serum monoclonal protein 25g/L, marrow plasma cells 5% (<10%), serum Ca 2.3 mmol/L, estimated GFR 100mL/min, Hb 12.5 g/dL, skeletal survey normal- normal kidney function

Elderly men

Weight loss, fatigue, hyperviscosity syndrome (visual problems, confusion, CCF

􏰂A low-grade NHL; lymphoplasmacytoid cells produce monoclonal serum IgM that infiltrates the LNs/BMmuscle weakness)

Treatment: plasmapheresis for hyperviscosity; chlorambucil,

cyclophosphamide and other chemo

Answer 134

Waldenstrom’s Macroglobinaemia (IgM)

Question 135

Aβ amyloid

Question 136

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

Answer 136

Smouldering multiple myeloma

Question 137

“Smouldering Myeloma”: >10% plasma cells (+ >30g/l) in BM but no CRAB / organ/tissue involvement

Answer 137

􏰂 No Rx required for both at this stage. Monitor for transformation.

Question 138

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

Answer 138

Multiple myeloma

Question 139

Abdo pain, serum monoclonal protein 10g/L, marrow plasma cells >10%, serum Ca 2.6 mmol/L, estimated GFR 30 mL/min, Hb 8 g/dL, lytic vertebral lesions

Answer 139

.

Multiple myeloma

Question 140

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.

Answer 140

CRAB

• young
• African
• fracture
• urine specific gtavity raised
• decreased GFR

Question 141

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

Answer 141

IgG

Question 142

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

Answer 142

IL-6

Question 143

Free light chains that are small enough to pass into the urine.

Answer 143

Bence-Jones protein

Question 144

Elevated levels imply a poor prognosis in myeloma patients.

Answer 144

Beta2 microglobulin and albumin levels to stage a patient’s disease into one of three stages. The only other factor that has been shown to impact significantly on outcome is age (and cytogenetics to some extent).

Question 145

Condition usually in asymptomatic elderly patients with a low level of paraprotein in the blood.

Answer 145

Monoclonal gammopathy of undetermined significance (MGUS)

Question 146

A 52 yr old woman who has a 5 yr history of rheumatoid arthritis and has recently been found to have proteinuria. Further examination revealed hepatosplenomegaly.

A rectal biopsy stained with Congo Red showed apple green birefringence in polarised light.

Answer 146

it is secondary as it is due to inflammatory conditions.

Question 147

A 60 yr old woman presents to her GP with fatigue and bone pain. Examination of her bone marrow demonstrated >10 % plasma cells, and a monoclonal protein in the serum (IgG) . Further investigations showed a hypercalcaemia (CRAB)

Answer 147

Multiple Myloma

Question 148

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.

Answer 148

􏰉Elderly men

􏰂A low-grade NHL; lymphoplasmacytoid cells** produce **monoclonal serum IgM that infiltrates the LNs/BM

􏰂 Weight loss, fatigue, hyperviscosity syndrome (visual problems, confusion, CCF, muscle weakness)

􏰂 Treatment: plasmapheresis for hyperviscosity; chlorambucil,

cyclophosphamide and other chemo

Question 149

A 73 yr old man is shown to have paraprotein in blood <2g/L. Further investigations reveal no renal impairment or bone destruction.

Answer 149

Monoclonal gammopathy of undetermined significance

(MGUS)

􏰂 No Rx required for both at this stage. Monitor for transformation.

MGUS: Monoclonal Gammaglobinopathy of Unknown Significance

􏰂 <10% plasma cells in marrow, <30g/l monoclonal paraprotein, no CRAB etc.

􏰂 Incidental finding; progresses to multiple myeloma at a rate of 1-2% / year

“Smouldering Myeloma”: >10% plasma cells (+ >30g/l) in BM but no CRAB / organ/tissue involvement

Question 150

A 60 yr old woman presents to her GP with shortness of breath and ankle oedema. When examined the patient has bilateral weakness and paraesthesia of her hands.

Investigations revealed a monoclonal proliferation of plasma cells and the presence of Bence Jones proteins.

Answer 150

Amyloidosis

Multisystem disorder caused by abnormal folding of proteins that are deposited as amyloid fibrils in tissues, disrupting their normal function.

Can be primary or secondary:

PRIMARY (AL amyloidosis)

● Most common

● Deposition of amyloid L protein

● Most associated with plasma cell dyscrasias and with paraproteins, e.g. multiple myeloma (although most don’t have multiple myeloma)

● Most have monoclonal Ig, free light chains in serum and urine (Bence Jones) and increased bone marrow plasma cells

Clinical features: caused by amyloid deposits in various organs:
(1) KIDNEY: nephrotic syndrome = most common presentation

(2) HEART: conduction defects, heart failure, cardiomegaly
(3) LIVER/SPLEEN: hepatosplenomegaly
(4) TONGUE: macroglossia in 10%
(5) NEUROPATHIES: including carpal tunnel

Question 151

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.

Answer 151

Benign paraproteinaemia

Question 152

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.

Answer 152

Multiple Myloma

Question 153

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.

Answer 153

Hairy Cell Lukemia - a subtype of CLL

Question 154

A 78 year old man is admitted to hospital after experiencing problems urinating and defecating. He also noticed numbness in some areas of his abdomen. Blood levels of calcium and ALP were raised. A bone scan confirms the diagnosis.

Answer 154

Bone metastasis

Question 155

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.

Answer 155

MM

Question 156

Corticosteroid refractory haemolytic anaemia

Answer 156

Splenectomy

Question 157

Chronic lymphocytic leukaemia managment

Answer 157

Cyclophosphamide, fludarabine and rituximab

Question 158

Chronic myeloid leukaemia (also known as chronic granulocytic leukaemia) treatment

Answer 158

Imatinib

Question 159

Polycythaemia rubra vera

Answer 159

Venesection and aspirin

Question 160

Multiple myeloma managment

Answer 160

Lenalidomide (Revlimid)

and low dose dexamethasone

followed by autologous stem cell transplant (SCT)

Question 161

Smouldering myeloma

Answer 161

Regular surveillance but no active treatment

Question 162

MGUS

Answer 162

Regular surveillance but no active treatment

Question 163

DiGeorge children are ineligible for this operation.

Answer 163

Thymectomy

Question 164

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

Answer 164

Campath (anti CD52, alemtuzumab)

Question 165

Anti-proliferative used in polycythaemia rubra vera and essential thrombocythaemia

Answer 165

Hydroxyurea

Question 166

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

Answer 166

Anagrelide

Question 167

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

Answer 167

Folate

Question 169

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

Answer 169

Leucovorin (Folinic acid, Formyl tetrahydrofolate)

Question 170

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

Answer 170

Rituximab (anti CD20)

Question 171

Add-on anti-proteasome drug for myeloma

Answer 171

Bortezomib (Velcade)

Question 172

Anti-proliferative used in PRV and essential thrombocythaemia

Answer 172

Hydroxyurea

Question 173

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

Answer 173

Anagrelide

Question 174

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

Answer 174

Folate

Question 175

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

Answer 175

Leucovorin (Folinic acid, Formyl tetrahydrofolate)

Question 176

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

Answer 176

Rituximab (anti CD20)

Question 177

case 4:

A 60 year old man with WCC 35x109/L and a peripheral blood film shows that these are lymphocytes.

Immunophenotype:

CD 19 + CD20 + CD10 - CD3 -

CD4 - CD5 + Kappa 2% Lambda 96%

Could someone please explain why this is B cell malignancy not T cell malignancy given that both B and T cell markers are present? I think the lecturer explained that but I didn’t catch that….

Answer 177

However in some malignant B cell development the malignant cells continue to aberrantly express CD5 as part of the disorganised malignant phenotype So short answer here is if you see a high lymphocyte count marking as B cells but aberrantly expressing CD5 think Chronic lymphocytic leukaemia. CLL prognostic factors are many but important ones are Immungolobulin gene configuration (mutated or unmutated) Zap 70 expression Cytogenetics (trisomy 12, del 13q or 17p

Question 178

Myeloma

Answer 178

Variable B cell

Question 179

Burkitts Lymphoma

Answer 179

Aggressive B cell

Question 180

ATLL

Answer 180

Aggressive T cell

Question 181

Most easily curable B cell neoplasm

Answer 181

Aggressive B cell

Question 182

Follicular lymphoma

Answer 182

Indolent B cell

Question 183

A 25 year old man presents with a single enlarged painless cervical lymph node (I) and complains of drenching night sweats (B symptoms) Histology shows the presence of Reed-Sternberg cells.

Answer 183

Hodgkins Disease Stage IB

Question 184

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

Answer 184

Burkitt’s Lymphoma

Question 185

During an insurance medical a 32 year old IT consultant was found to have hilar lymphadenopathy on his chest x-ray.

He also complains of a painless lump under his right arm.

Answer 185

Hodgkins Stage IIA

Question 186

Advanced Hodgkins disease should be treated with…..

Answer 186

Combination Chemotherapy

Question 187

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

Answer 187

ABVD combination chemotherapy + radiotherapy if required

Question 188

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

Answer 188

Burkitt’s Lymphoma

Question 189

A classical but rare constitutional symptom of Hodgkin lymphoma.

Answer 189

Pel Ebstein Fever

Question 190

The stage characterised by multiple lymph node involvement 2 on the same side of the diaphragm but without constitutional symptoms A

Answer 190

2A

Question 191

The grade of the Follicular lymphoma NHL subtype.

Answer 191

Indolent

Question 192

A patient presents with a lump in his groin and complains of night sweats and an itchy rash.

A biopsy is taken and on inspection is shown to include Reed-Sternberg cells.

Answer 192

Hodgkin lymphoma

Question 193

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.

Answer 193

Polymalagia Rheumatica

Question 194

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?

Answer 194

Leucoerythroblastic anaemia

Question 195

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?

Question 196

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?

Answer 196

Monocytes

Question 197

Anaemia and neutropenia are more common in which of the above autoimmune disease?

Answer 197

Systemic lupus erythematosis

Question 198

A peripheral blood smear of a thrombocytopenic patient raised Lactate dehydrogenase and unconjugated bilirubin shows fragmented Red blood cells.

Answer 198

Question 199

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

Answer 199

Secondary true polycythaemia

Question 200

Monocytosis but with a normal neutrophil count.

Answer 200

Brucella infection

Question 201

A markedly raised haemoglobin in a patient with splenomegaly

Answer 201

Polycythaemia vera

Question 202

is an inherited condition which results in X being resistant to degradation by activated Protein C; this predisposes affected individuals to development of clots.

Answer 202

Factor V Leiden

Question 203

A peripheral blood smear of a thrombocytopenic patient raised Lactate dehydrogenase and unconjugated bilirubin shows fragmented Red blood cells.

Answer 203

Microangiopathic haemolytic anaemia

Question 204

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

Answer 204

Secondary true polycythaemia

Question 205

Monocytosis but with a normal neutrophil count.

Answer 205

Brucella infection

Question 206

A markedly raised haemoglobin in a patient with splenomegaly

Answer 206

Polycythemia Rubra Vera

Question 207

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

Answer 207

Acute fungal infection

Question 208

A patient with a positive coombs test and a blood film showing spherocytes.

Answer 208

Question 209

A 30 year old female presents to her GP complaining of aches and pains in her joints and a rash on her face after returning from a holiday in Spain.

Her blood tests show a normocytic anaemia, an elevated ESR and a positive Anti-Nuclear Antibodies test.

Answer 209

SLE

Question 210

A 22 year old female who has recently undergone surgery presents with difficulties breathing and swelling of the face, hands and feet. She also complains of severe abdominal pains. She has experienced similar problems in the past.

Answer 210

Hereditary angioedema

Hereditary angioedema is an AD condition associated with low plasma levels of the C1 inhibitor (C1-INH) protein.

C1-INH is a multifunctional serine protease inhibitor - the probable mechanism behind attacks is uncontrolled release of bradykinin resulting in oedema of tissues.

Investigation

C1-INH level is low during an attack

low C2 and C4 levels are seen, even between attacks. Serum C4 is the most reliable and widely used screening tool

Symptoms

• attacks may be proceeded by painful macular rash
• painless, non-pruritic swelling of subcutaneous/submucosal tissues
• may affect upper airways, skin or abdominal organs (can occasionally present as abdominal pain due to visceral oedema)
• urticaria is not usually a feature

Management

• acute: IV C1-inhibitor concentrate, fresh frozen plasma (FFP) if this is not available
• prophylaxis: anabolic steroid Danazol may help

Question 211

A 16 year old male is rushed into A+E with severe SOB and wheezing.

He is also noted to have urticaria and he is tachycardic and hypotensive with decreasing consciousness.

Answer 211

Anaphylaxis

Question 212

antibodies Sjorgen

Answer 212

Anti-Ro, Anti-La antibody (speckled pattern), 60-70% have positive RF

Question 213

scleroderma antibodies

Answer 213

Question 214

A 25 year old man presents with a single enlarged painless cervical lymph node (I)and complains of drenching night sweats (B). Histology shows the presence of Reed-Sternberg cells.

Answer 214

Hodkin stage IB

Question 215

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

Answer 215

Question 216

During an insurance medical a 32 year old IT consultant was found to have hilar lymphadenopathy on his chest x-ray. He also complains of a painless lump under his right arm.

Answer 216

Hodgkins Stage IIA

Question 217

Advanced Hodgkins disease should be treated with…..

Answer 217

Combination Chemotherapy

Question 218

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

Answer 218

Radiation Therapy Alone