Clinical SBAs
Clinical Haematology: (21 questions)

Questions

• 1
  A 5-year old boy is diagnosed with sickle-cell disease. Which of the following is not a complication?
  Difficulty: Medium     Topic: Sickle cell disease complication
  a

  High flow priapism

  b

  Stroke

  c

  Pulmonary hypertension

  d

  Osteonecrosis

  e

  Leg ulcers
  Explanation: When HbS becomes deoxygenated it polymerises, which causes RBC to occlude vessels. These are ischaemic crisis that are very painful; usually limbs, spleen, mesentery or cerebral vessels (causing stroke). It if occurs in the corpora cavernosa then it causes low-flow priapism. High flow priapism is due to an arterial-venous malformation post-trauma. Pulmonary hypertension develops due to relative hypoxia in the lungs. Infarction of the femoral head is common (osteonecrosis). Ischaemic leg ulcers can be severe.
• 2
  Which of the following drug – side effect pairs is incorrect?
  Difficulty: Hard     Topic: Side effects of immunosuppressants
  a

  Azathioprine - retinopathy

  b

  Cyclophosphamide - haemorrhagic cystitis

  c

  Ciclosporin - nephrotoxicity

  d

  Methotrexate - oral ulcers

  e

  Prednisolone - pancreatitis
  Explanation: Azathioprine can cause bone marrow suppression and raised LFTs. Hydroxychloroquine and ethambutol commonly cause retinopathy. Cyclophosphamide results in haemorrhagic cystitis (unless thiol-mensa is given along side), other effects: teratogenesis, can cause pancytopenia and infertility. Ciclosporin causes dose-dependent chronic nephrotoxicity or an acute renal failure; it also increases risk of skin cancer. Methotrexate causes oral ulcers, teratogenicity, myelosuppression and hepatic and pulmonary fibrosis. Steroids can cause acute pancreatitis.
• 3
  A previously well 30-year old lady suffers a DVT in her right arm and is found to have a hereditary thrombophilia. What is the most likely cause?
  Difficulty: Medium     Topic: Arm DVT
  a

  Prothrombin gene mutation

  b

  Protein S deficiency

  c

  Antithrombin deficiency

  d

  Factor V Leiden mutation

  e

  Protein C deficiency
  Explanation: Venous thromboses in the upper limbs is suggestive of a thrombophilia. This could occur with any of the options listed however factor V Leiden mutation is by far the most frequent. This causes excessive thrombotic and reduced fibrinolytic action of FVa. Protein C and S are normally involved in anti-thrombotic mechanisms therefore mutation increases the risk of thrombosis. Anti-thrombin acts to prevent thrombin activation. Prothrombin mutation allows excessive production of active thrombin.
• 4
  A 82-year old man presents with back pain. Multiple osteolytic lesions are seen on skeletal survey and bone marrow trephine shows 34% monoclonal cells. What is the most appropriate initial management?
  Difficulty: Hard     Topic: Back pain and osteolysis
  a

  Full intensity allogenic bone marrow transplant

  b

  Full intensity autologous bone marrow transplant

  c

  Reduced intensity autologous bone marrow transplant

  d

  Radical radiotherapy

  e

  Chemotherapy
  Explanation: This man has myeloma, which should be suspected in elderly patients presenting with back pain, especially if there is anaemia or hypercalcaemia. >30% monoclonal plasma cells in the bone marrow is highly suggestive of myeloma. This man is too old for a full-intensity or allogenic transplant, due to the high mortality. However reduced intensity autologous transplant may be attempted but this is only after initial chemotherapy. Palliative radiotherapy can be used to treat painful bone lesions but radical radiotherapy is not part of myeloma treatment apart from total body irradiation pre-bone marrow transplant.
• 5
  A 67-year old man presents with inguinal and cervical lymphadenopathy. Hb 9.1g/L, platelets 120×10^9/L, WCC 114×10^9/L. What is the most likely diagnosis?
  Difficulty: Medium     Topic: 67-year old with lymphadenopathy
  a

  Multiple myeloma

  b

  High grade non-Hodgkin's lymphoma

  c

  Chronic lymphocytic leukaemia

  d

  Chronic myeloid leukaemia

  e

  Acute lymphocytic leukaemia
  Explanation: CLL presents a little older than CML and the WCC is not as high. Generalised lymphadenopathy in CLL is common however a third of all diagnoses are incidental, usually finding a raised WCC on routine bloods. The blood film would demonstrate many small mononuclear cells. Prognosis varies from 1 to >10yrs depending peripheral blood counts at presentation. There is no treatment while asymptomatic. Death results from infection or Richter's transformation to an acute leukaemia. Multiple myeloma would not cause a WCC this high and there are none of the other features associated: hypercalcaemia, renal failure, lytic bone lesions or infection. High-grade NHL is less likely to give disseminated lymphadenopathy at presentation and the patient would present systemically unwell. Peripheral blood counts are usually normal in low-grade NHL. CML causes a thrombocythaemia, rather than low platelets as in this case. Also lymphadenopathy is rare in CML. ALL is uncommon in adults and would present with features of bone marrow failure rather than asymptomatic lymphadenopathy.
• 6
  A 45-year old man presents with fatigue, weight loss and splenomegaly. Hb 10.0g/L, platelets 852×10^9/L, WCC 282×10^9/L. What is the most likely diagnosis?
  Difficulty: Easy     Topic: 45-year old with splenomegaly
  a

  Multiple myeloma

  b

  Low grade non-Hodgkin's lymphoma

  c

  Chronic lymphocytic leukaemia

  d

  Chronic myeloid leukaemia

  e

  Acute myeloid leukaemia
  Explanation: CML characteristically presents with a greatly raised WCC and massive splenomegaly; thrombocythaemia is common at diagnosis. It is most common at 40-50yrs and begins in a chronic phase, which can be controlled with imatinib. Ultimately it undergoes transformation into a blast crisis, resulting in rapid death. None of the other diagnoses would give such a high WCC. CLL causes low platelets, unlike in this patient, and the WCC would be nearer 100-200x109/L. In practice CLL and CML are most easily differentiated by examination of the white-cell count; CLL causes a lymphocytosis and CML causes a neutrophilia.
• 7
  A 68-year old man presents with an intracerebral bleed. Hb 6.6g/L, platelets 17×10^9/L, WCC 98×10^9/L. What is the most likely diagnosis?
  Difficulty: Medium     Topic: 68-year old with intracerebral bleed
  a

  Multiple myeloma

  b

  Hodgkin's lymphoma

  c

  Acute lymphocytic leukaemia

  d

  Acute myeloid leukaemia

  e

  Low grade non-Hodgkin's lymphoma
  Explanation: AML is most common in the elderly and presents with anaemia and thrombocytopenia with raised peripheral WCC. It may occur secondary to myelodysplasia or CML. Prognosis is poorer due to the age of patients with many not suitable for bone marrow transplant. Multiple myeloma rarely presents with a raised white cell count and thrombocytopenia is not commonly seen at presentation. Lymphadenopathy is less commonly a feature of Hodgkin's and NHL. ALL is less common over middle-age and usually presents with a low WCC.
• 8
  A 8-year old boy presents with purpuric bruising on his abdomen and arms. Hb 8.1g/L, platelets 80×109/L, WCC 4×10^9/L. What is the most likely diagnosis?
  Difficulty: Easy     Topic: 8-year old with purpura
  a

  Acute myeloid leukaemia (AML)

  b

  Acute lymphoblastic leukaemia (ALL)

  c

  Burkitt's lymphoma

  d

  Hodgkin's lymphoma

  e

  Low grade non-Hodgkin's lymphoma (NHL)
  Explanation: ALL is the most common leukaemia of childhood and presents with a peripheral pancytopenia; raised WCC at presentation is less common and a poor prognostic marker. CNS involvement is common and intra-thaecal methotrexate is used prophylactically. Overall survival rate is high. The incidence of AML increases with age. Burkitt's (a high-grade NHL) and Hodgkin's lymphoma present with lymphadenopathy. Low-grade NHL presents with systemic features and palpable lymph nodes with hepatosplenomegaly.
• 9
  A 40-year old man on warfarin for AF attends to have his INR checked. He is asymptomatic but his INR is 5. What is the most appropriate management?
  Difficulty: Hard     Topic: Over-anticoagulation
  a

  Continue with next warfarin dose

  b

  Omit warfarin till INR has fallen

  c

  Oral vitamin K

  d

  Give fresh frozen plasma

  e

  Give prothrombin complex concentrate
  Explanation: Target INR on warfarin is 2-3 for all indications except for metallic heart valves, where 3-4 is used. If INR is <6 then warfarin can be reduced or stopped until back within range. If >8 or only minor bleeding then warfarin should be stopped and oral vitamin K can be given. If there is major bleeding then 1st line is prothrombin complex concentrate, with IV vitamin K. FFP is given if this is not available.
• 10
  Which of the following is not a side-effect of low molecular weight heparin (LMWH)?
  Difficulty: Easy     Topic: Heparin side-effects
  a

  Thrombocytosis

  b

  Osteoporosis

  c

  GI bleed

  d

  Subdural haemorrhage

  e

  Intracranial haemorrhage
  Explanation: LMWH is used for: initial treatment of PE and DVT, prophylaxis against VTE for in-patients and pregnant women at high risk, and in treatment of MI. The main side effects are: increased risk of bleeding, osteoporosis and thrombocytopenia.
• 11
  A Greek 24-year old man is incidentally found to have Hb 10.5g/dl and MCV 64fl. Iron studies are normal. What is the most likely cause?
  Difficulty: Medium     Topic: Greek man with low MCV
  a

  Beta thalassaemia major

  b

  Beta thalassaemia minor

  c

  Hereditary spherocytosis

  d

  Sickle cell disease

  e

  Hereditary elliptocytosis
  Explanation: Thalassaemia is most common in the Mediterranean and Asia. Beta thalassamaemia is due to a point-mutation in the beta-chain of Hb. Heterozygosity (beta-thalassaemia 'minor') causes asymptomatic microcytic anaemia with a disproportionately low MCV - contrasting it from SCD and iron-deficiency anaemia. Beta-thalassaemia minor major requires multiple transfusions and there is extramedullary haematopoiesis. Spherocytosis and elliptocytosis cause high-normocytic anaemia.
• 12
  Which of the following statements is not true?
  Difficulty: Easy     Topic: Causes of anaemia
  a

  Cardiac valve replacement may result in haemolysis

  b

  Massive blood loss does not cause anaemia <30min

  c

  Phenytoin causes a macrocytic anaemia

  d

  Severely anaemic patients may be centrally cyanosed

  e

  Anaemia can cause high-output cardiac failure
  Explanation: Peripheral cyanosis is due to presence of >2.5g/dl deoxygenated haemoglobin, therefore anaemic patients are less likely to be cyanosed than those with polycythaemia. Prosthetic valves can cause shear stress, especially in high cardiac output states. Acute exsanguination results in equal loss of red cells and plasma therefore there is no anaemia until interstitial fluid is gradually reabsorbed into the circulation, which can take up to 24hours for full effects to be seen. Phenytoin is an anti-folate therefore can cause a megaloblastic anaemia. High-output cardiac failure occurs when demands are not met output is normal, other causes include: beriberi, thyrotoxicosis and Paget's disease.
• 13
  A 37-year old lady with SLE presents with a normocytic anaemia and reticulocytosis. The direct Coombs’ test is positive. What is the most likely diagnosis?
  Difficulty: Medium     Topic: SLE, anaemia and reticulocytosis
  a

  Paroxysmal nocturnal haemoglobinuria

  b

  Glucose-6-phosphate dehydrogenase (G6PD) deficiency

  c

  Hereditary spherocytosis

  d

  Pyruvate kinase deficiency

  e

  Autoimmune haemolysis
  Explanation: Direct Coomb's test looks for the presence of antibodies bound to RBC in circulation, which cause extravascular haemolysis. AIHA is the only option that gives a positive direct Coombs' test. The indirect Coombs' is due during cross-match to look for circulating antibodies in serum. PNH causes complement-mediated haemolysis at night and thrombosis. G6PD-deficiency makes RBC susceptible to haemolysis with aspirin, fava beans or illness. Pyruvate kinase deficiency is asymptomatic unless homozygotic, in which case it causes neonatal haemolysis and jaundice.
• 14
  A 75-year old lady with surgically corrected aortic valve disease presents with fatigue. Hb 8.7g/dl, MCV 82fl. Peripheral film show schistocytes. What is the most likely diagnosis?
  Difficulty: Hard     Topic: Aortic valve replacement and anaemia
  a

  Paroxysmal nocturnal haemoglobinuria (PNH)

  b

  Non-immune mediated haemolytic anaemia

  c

  Hereditary spherocytosis

  d

  Autoimmune haemolytic anaemia (AIHA)

  e

  Paroxysmal cold haemoglobinuria (PCH)
  Explanation: Schistocytes are fragmented red blood cells that occur due to shear stress, which causes a high-normocytic anaemia. They can also be due to microangiopathic haemolytic anaemia, a condition where fibrin deposition and thrombi in small vessels result in haemolysis. MAHA can be caused by: DIC, thrombotic thrombocytopenic purpura and haemolytic uraemic syndrome. PNH occurs due to hereditary susceptibility of RBC to complement-lysis, especially at night, with anaemia and increased thrombosis risk. Hereditary spherocytosis causes extravascular haemolysis with mild anaemia. AIHA is from antibodies against the RBC membrane with positive Coombs' test. PCH is due to reactive antibodies post-infection, and is also Coombs' positive.
• 15
  A 48-year old woman has Hb 8.1g/dl with MCV 110fl. Which of the following medications is she least likely to be taking?
  Difficulty: Hard     Topic: Drug causes of anaemia
  a

  Phenytoin

  b

  Carbimazole

  c

  Amiodarone

  d

  Hydroxycarbamide

  e

  Methotrexate
  Explanation: There are many drug causes of macrocytic anaemia including: anti-folates (methotrexate and phenytoin), cytotoxic drugs (hydroxycarbamide and 5-FU), amiodarone can cause hypothyroidism with macrocytic anaemia. Carbimazole risks agranulocytosis but not anaemia.
• 16
  A 62-year old man has Hb 6.5g/dl. Which of the following is least likely to be present?
  Difficulty: Easy     Topic: Severe anaemia
  a

  Pan-systolic murmur

  b

  Angina

  c

  Palpitations

  d

  Bounding pulse

  e

  Headache
  Explanation: Severe anaemia can cause high cardiac output to compensate for poor tissue oxygenation (which may lead to heart failure). This may generate an ejection systolic flow murmur over the aortic valve (even with a normal valve), not pan-systolic. Other features of the hyperdyamic circulation are: palpitations, bounding pulse and headache. Cardiac ischaemia can cause angina even in the absence of coronary artery disease and anaemia will exacerbate angina caused by atherosclerosis.
• 17
  A 22-year old man with diarrhoea and weight loss is diagnosed with Coeliac’s disease and is found to have Hb 9.9g/dl and MCV 87fl. What is the most likely cause of his anaemia?
  Difficulty: Easy     Topic: Diarrhoea and weight loss
  a

  Autoimmune haemolysis

  b

  Haemoglobinopathy

  c

  Concomitant hypothyroidism

  d

  Medication side effect

  e

  Deficiency of raw materials
  Explanation: This man has a mixed deficiency anaemia due to malabsorption. At diagnosis it is common for patients with Coeliac's to have deficiency in iron, folate and/or B12, therefore the MCV can be normal. Autoimmune haemolysis and some medications may produce a normocytic anaemia but the history makes mixed deficiency the most likely diagnosis. Haemoglobinopathies cause microcytic anaemias and hypothyroidism causes a macrocytic anaemia.
• 18
  A 57-year old woman presents with a microcytic, hypochromic anaemia and a history of altered bowel habit. Which of the following is least likely to be present?
  Difficulty: Easy     Topic: Microcytic anaemia
  a

  Atrophic glossitis

  b

  Leukonychia

  c

  Angular chelosis

  d

  Post-cricoid web

  e

  Raised total iron binding capacity
  Explanation: This woman has iron-deficiency anaemia (IDA) due to GI bleeding. Leukonychia are white nails from nail bed oedema in hypoalbuminaemia. Atrophic glossitis is inflammation of the tongue without hypertrophy (unlike in B12 deficiency). Angular chelosis (or stomatitis) is cracking at angle of the mouth. A post-cricoid web is a feature of Plummer-Vinson (Patterson-Brown-Kelly) syndrome that is associated with IDA. Raised TIBC reflects transferrin levels, which increase to maximise iron carrying ability in the blood.
• 19
  A 37-year old woman has a Hb 7.9g/dL. MCV 95fl, ferritin 98mcrg/L, total iron binding capacity 58mcrmol/L, lactate dehydrogenase 370IU/L. What is the most likely cause?
  Difficulty: Medium     Topic: Causes of anaemia 1
  a

  Hypersplenism

  b

  Autoimmune haemolytic anaemia (AIHA)

  c

  Thalassaemia

  d

  Sickle cell disease (SCD)

  e

  Pernicious anaemia
  Explanation: This woman has a high-normocytic anaemia with raised lactate dehydrogenase. AIHA occurs due to autoantibodies directed against the RBC membrane that cause (usually) extravascular haemolysis. Hypersplenism as the primary cause of anaemia is due to sequestration more than haemolysis therefore LDH will not be as markedly raised. Thalassaemia and SCD cause a microcytic anaemia. Pernicious anaemia causes a macrocytic anaemia.
• 20
  Which of the following is not a cause of macrocytic anaemia?
  Difficulty: Easy     Topic: Macrocytic anaemia causes
  a

  Anaemia of chronic disease

  b

  Myelodysplasia

  c

  Haemolysis

  d

  Folate deficiency

  e

  Hypothyroidism
  Explanation: Anaemia of chronic disease is a condition associated with many inflammatory conditions. It results in either a normocytic or microcytic anaemia, which can mimic iron deficiency however ferritin is normal or raised. It occurs due to a failure to utilise iron and incorporate it into RBC, which results in hypochromic red cells. Myelodysplasia is a condition where bone marrow haematopoiesis does not proceed normally, which results in abnormal cells of one or several lineages. Folate is needed for synthesis of nucleic acid and its deficiency results in megaloblastic anaemia. This occurs when the rate of development of the nucleus is slower than that of the rest of the cell. This is seen by multi-segmented neutrophil nuclei and pancytopenia. Myelodysplasia, haemolysis and hypothyroidism do cause anaemia with raised MCV without megaloblasts. Haemolysis causes increased MCV due to raised reticulocyte count, which have a higher volume than RBC.
• 21
  A 69-year old man presents with purpuric bleeding over his abdomen and arms; examination is otherwise normal. FBC shows a pancytopenia. Which investigation is most likely to give the diagnosis?
  Difficulty: Medium     Topic: Purpura and pancytopenia
  a

  Peripheral blood smear

  b

  Bone marrow trephine

  c

  Bone marrow aspirate

  d

  Lymph node biopsy

  e

  Peripheral blood phenotyping and immunohistochemistry
  Explanation: This man has a bone-marrow pathology causing pancytopenia. Potential diagnoses include myelodysplasia, aplastic anaemia and acute myeloblastic leukaemia. A bone marrow trephine is required, rather than aspirate, because the architecture needs to be examined for increased fat and hypocellularity if aplastic anaemia or myelodysplasia are to be differentiated. Allogenic bone marrow transplant is the treatment of choice for young patients with aplastic anaemia. Myelofibrosis is a less likely diagnosis because the majority of patients have massive splenomegaly at presentation. If the cause were infiltrative leukaemia then bone marrow aspirate would may give the diagnosis but a trephine has the highest diagnostic rate of the investigations listed.