A. Von Willebrand disease
B. Disseminated intravascular coagulation (DIC)
C. Acquired factor VIII inhibitor
D. Chronic liver disease
E. Haemophilia B
14. A 78-year-old woman is found incidentally to have a lymphocyte count of 20.0 × 109/L (0.5–3.5 × 109 cells/L) on full blood count examination before her elective right knee replacement. On examination, there is no lymphadenopathy, splenomegaly or hepatomegaly. Her haemoglobin is 114 g/L (115–155 g/L) and platelet count is 220 × 109/L (120–400 × 109 cells/L). Lymphocyte surface markers reveal expression of CD5, CD19, CD20 and CD28. What management should she receive?
A. Chlorambucil after bone marrow biopsy
B. Alemtuzumab after computed tomography scan for staging
C. Observation without bone marrow biopsy
D. Fludarabine without bone marrow biopsy
E. Lenalidomide after molecular study
15. A 32-year-old woman presents to the emergency department with an 8-h history of severe right upper quadrant pain. An abdominal ultrasound reveals several mobile gallstones and gallbladder wall thickening, which is consistent with acute cholecystitis. The liver is unremarkable but the spleen measures 14 cm. The cholecystitis improves with conservative management. On further questioning, she tells you that her father had his spleen removed. The results of investigations and the blood film are shown below. Which one of the following tests is the most appropriate next investigation?
| Value | Reference range | |
|---|---|---|
| Haemoglobin (g/L) | 111 | 115–155 |
| Mean corpuscular volume (fL) | 101 | 80–98 |
| White blood cells (/L) | 8.1 × 109 | 4.0–11.0 × 109 |
| Platelet count (/L) | 190 × 109 | 150–400 × 109 |
| Reticulocyte count (%) | 7 | 1–3 |
| Bilirubin (μmol/L) | 27 | 2–24 |
A. Autoimmune profile
B. Bone marrow biopsy
C. Coombs test
D. Osmotic fragility test
E. Haemoglobin electrophoresis
16. Which one of the following is correct in a patient with severe aplastic anaemia?
A. Patients with severe aplastic anaemia usually present with severe infection at initial presentation
B. Megakaryocytes are not helpful in distinguishing myelodysplastic syndrome from severe aplastic anaemia
C. Aplastic anaemia and paroxysmal nocturnal haemoglobinuria rarely overlap (<1% of cases)
D. The appearance of bone marrow in inherited and acquired aplastic anaemia is identical
E. Change in leucocytes telomere length is not associated with severe aplastic anaemia
17. A 60-year-old man has recently been diagnosed with B-cell non-Hodgkin lymphoma. He is waiting for chemotherapy to commence in 2 days. He suddenly develops headache, confusion, visual deterioration and epistaxis. Fundoscopy reveals retinal haemorrhages. Which one of the following investigations should be included in the evaluation?
A. Complement levels
B. C-reactive protein
C. Plasma electrophoresis
D. Serum free light chains
E. Serum viscosity
18. Which one of the following factors should be taken into account when determining the dose of an iron-chelating agent in a patient who is red blood cell transfusion dependent because of myelodysplastic syndrome?
A. Presence of cardiac iron overload
B. Presence of splenomegaly
C. Haemoglobin level
D. Mean corpuscular volume
E. Pain at the site of subcutaneous infusion
19. Which one of the following statements best describes the role of 18F-fluorodeoxyglucose (18F-FDG) positron emission tomography (PET) in the evaluation of adults with Hodgkin lymphoma?
A. Detects metabolically inactive tumour tissue
B. Determines the most appropriate combination chemotherapy
C. Diagnosis of the condition
D. Disease staging
E. Identifies patients who need chemotherapy only
20. A 34-year-old primigravida is found to have a low platelet count (see below) on a full blood examination performed at 34 weeks of gestation. Her platelet count was 180 x109/L at 12 weeks of gestation. She has no significant past medical history and is not taking any medications. Her blood pressure is 105/70 mmHg. Her other investigation results are shown below. Her liver function tests are normal. Which of one of the following is the most likely cause of her thrombocytopenia?
| Value | Reference range | |
|---|---|---|
| Haemoglobin (g/L) | 108 | 115–160 |
| White blood cell count (cells/L) | 4.3 × 109 | 3.2–11.0 × 109 |
| Platelet count (cells/L) | 80 × 109 | 150–450 × 109 |
| Mean corpuscular volume (fL) | 80 | 82–98 |
| Reticulocyte count (%) | 1.8 | 0.8–2.0 |
| Urinary analysis (mg/L) | Protein 30 | Negative |
| Serum creatinine (μmol/L) | 61 | 70–110 |
| Lactate dehydrogenase (IU/L) | 173 | 70–250 |
A. Haemolysis, elevated liver enzymes and low platelet (HELLP) syndrome
B. Pre-eclampsia
C. Evan syndrome
D. Thrombotic thrombocytopenic purpura
E. Gestational thrombocytopenia
21. A 52-year-old woman who had an ischemic stroke 12 months ago but no residual neurological deficits was referred for evaluation of recurrent episodes of proximal deep venous thrombosis (DVT) of the lower limbs in the last 10 months. The results of investigations are shown below. A bone marrow biopsy showed a mild hyperplasia of erythrocytic bone marrow. Urine dipstick for blood was +++. What is the most likely diagnosis?
| Value | Reference range | |
|---|---|---|
| Haemoglobin (g/L) | 82 | 115–155 |
| Mean corpuscular volume (fL) | 98 | 80–98 |
| Mean corpuscular haemoglobin (pg) | 31 | 27–33 |
| White blood cells (cells/L) | 4.0 × 109 | 4.0–11.0 × 109 |
| Platelet count (cells/L) | 93 × 109 | 150–400 × 109 |
| Reticulocytes (%) | 5.4 | 0.5–1.5 |
| Total bilirubin (μmol/L) | 50 | 2–24 |
| Lactate dehydrogenase (U/L) | 944 | 110–230 |
| Coombs test | Negative |
A. Anti-thrombin III deficiency
B. Haemolytic uraemic syndrome
C. Paroxysmal nocturnal haemoglobinuria
D. Homocysteinaemia
E. Protein C deficiency
22. Which one of the following factors is the most important risk factor for acute graft-versus-host disease after allogeneic haemopoietic cell transplantation?
A. Age of the recipient
B. CD4+ cell count in the recipient at time of transplantation
C. Cytomegalovirus status of recipient
D. Mismatch between donor and recipient in human leucocyte antigens (HLAs)
E. Total CD34+ cells transplanted
23. Which one of the following best describes rituximab use in the treatment of B-cell lymphomas?
A. Rituximab is only used as a single agent
B. Rituximab is a chimeric monoclonal antibody that recognises human CD38 antigen
C. Patients should be screened for Epstein–Barr virus before rituximab treatment
D. Rituximab when combined with chemotherapy improves progression-free survival of aggressive non-Hodgkin lymphoma
E. Rituximab-induced lymphopenia usually lasts more than 18 months
24. A 65-year-old woman with headache, flushing and unexplained (anaphylactoid) shock was found to have a high serum tryptase level. Collateral history from her husband revealed previous allergic reactions to multiple medications, including penicillin, cephalosporins and aspirin. Which one of the following tests is the cornerstone of diagnosis this patient’s condition?
A. Lymphocyte surface markers
B. Radioallergosorbent test (RAST)
C. Cytogenetic study
D. Bone marrow biopsy
E. Rechallenge the patient with the medications that she was allergic to
25. A 54-year-old obese woman presents with extensive deep venous thrombosis of her left leg. She has a family history of venous thromboembolism. She was started on low-molecular-weight heparin and warfarin 10 mg daily for 2 days. Within 72 h, she developed necrotic-looking skin lesions on her thighs without trauma. What underlying condition is she most likely to have?
A. Anti-thrombin III deficiency
B. Protein S deficiency
C. Anti-phospholipid syndrome
D. Protein C deficiency
E. Homozygous factor V Leiden mutation
26. A 58-year-old man presents with a 3-month history of worsening breathlessness, confusion, headache and bleeding gums. His investigation results are shown below. Bone marrow biopsy reveals marrow infiltration by small lymphocytes showing plasma cell differentiation. What is the next appropriate treatment for this patient?
| Value | Reference range | |
|---|---|---|
| Haemoglobin (g/L) | 95 | 135–175 |
| White cell count (cells/L) | 3.0 × 109 | 4.0–11.0 × 109 |
| Platelet count (cells/L) | 135 × 109 | 150–450 × 109 |
| IgA (g/L) | 3.0 | 0.9–3.4 |
| IgG (g/L) | 6.0 | 5.0–16.0 |
| IgM (g/L) | 31.0 | 0.5–3.0 |
| Serum viscosity (cP) | 4.2 | 1.3–1.8 |
A. Chlorambucil
B. Cyclophosphamide
C. Plasma exchange
D. Rituximab
E. Thalidomide
27. Epstein–Barr virus is associated with which of the following subtypes of non-Hodgkin lymphoma?
A. Gastric mucosa-associated lymphoid tissue lymphoma
B. Follicular lymphoma
C. Nasal natural killer cell lymphoma
D. Chronic lymphocytic leukaemia
E. Splenic marginal-zone lymphoma
28. Which one of the following is used to treat mild haemophilia A without the risk of transmitting infectious diseases?
A. Factor VIII concentrate
B. Factor IX concentrate
C. Prothrombin complex concentrate
D. Tranexamic acid
E. Desmopressin
29. Which one of the following is correct concerning atypical haemolytic uraemic syndrome (aHUS)?
A. It is only an acute disease
B. It is predominantly (>80%) a condition affecting children
C. It is associated with mutations in genes encoding complement regulatory proteins
D. It is due to mutations in the gene encoding ADAMTS13
E. Plasma exchange is the only effective treatment
30. The results of a patient’s biochemistry profile after chemotherapy for Burkitt lymphoma are shown below. He was transferred to the intensive care unit for cardiac monitoring and treatment. Which one of the following treatment options should be used to lower uric acid level?
| Value | Reference range | |
|---|---|---|
| Potassium (mmol/L) | 6.8 | 3.4–4.5 |
| Phosphate (mmol/L) | 2.4 | 0.70–0.95 |
| Corrected calcium (mmol/L) | 1.60 | 2.10–2.55 |
| Urate (mmol/L) | 0.87 | 0.45–0.60 |
| Creatinine (μmol/L) | 348 | 60–120 |
A. Aggressive intravenous diuretics
B. Allopurinol
C. Rasburicase
D. Urinary alkalinisation
E. Prednisolone
31. A 68-year-old woman is recovering from an elective knee replacement surgery for osteoarthritis. She has been receiving unfractionated heparin 5000 units twice a day. On day 10 she is breathless and computed tomographic pulmonary angiography shows bilateral pulmonary embolism. Laboratory investigation reveals a haemoglobin of 95 g/L (115–155 g/L) and platelet count of 45 × 109 cells/L (150–450 × 109 cells/L). What additional diagnostic investigation should be undertaken?
A. Extractable nuclear antibodies
B. Activated partial thromboplastin time
C. Anti-phospholipid antibodies
D. Anti-platelet factor-4/heparin antibodies
E. Anti-thrombin III levels
Theme: Anaemia (for Questions 32–35)
A. Haemolytic anaemia
B. Pure red cell aplasia
C. Iron-deficiency anaemia
D. Pernicious anaemia
E. Beta-thalassaemia minor
F. Sideroblastic anaemia
G. Anaemia of chronic disease
H. Sickle cell disease
32. Which disorder is predisposed to salmonella osteomyelitis?
33. A 30-year-old woman with known hypoparathyroidism and Addison disease has been found to have a mutation in the autoimmune regulator (AIRE) gene and has become progressively anaemic. What cause of anaemia should be considered?
34. A 70-year-old woman with a 10-year history of myasthenia gravis adequately controlled with pyridostigmine, presents with general fatigue secondary to severe anaemia [haemoglobin of 62 g/L (115–155 g/L)]. A computed tomography (CT) scan of the thorax revealed the presence of an anterior mediastinal mass. Bone marrow aspirate showed severe erythroid hypoplasia associated with normal myeloid and megakaryocytic cell lines. What is the most likely diagnosis?
35. A 29-year-old man presents with an 8-day history of fever and productive cough. The patient was previously healthy and was not using any drugs. On physical examination, the patient appears ill and his temperature is 39.8o C. Chest examination showed bilateral basal crackles. The results of initial investigations are shown below. His chest X-ray shows bilateral basal opacities. Anti-mycoplasma antibody titre by complement fixation was high at 1:10 240. What is the most likely cause of his anaemia?
| Value | Reference range | |
|---|---|---|
| Haemoglobin (g/L) | 93 | 115–155 |
| Mean corpuscular volume (fL) | 94 | 80–98 |
| Mean corpuscular haemoglobin (pg) | 31 | 27–33 |
| White blood cells (cells/L) | 18.1 × 109 | 4.0–11.0 × 109 |
| Platelet count (cells/L) | 203 × 109 | 150–400 × 109 |
| Reticulocytes (%) | 3.4 | 0.5–1.5 |
| Lactate dehydrogenase (U/L) | 758 | 110–230 |
Answers
Basic Science
1. Answer D
For an adult to maintain a normal red blood cell count, about 2–3 million new red blood cells are produced every second. For severe forms of thalassaemia, many erythroblasts and mature red blood cells are damaged, increasing erythropoiesis by 20–30 times.
At a molecular level, haemoglobin synthesis is controlled by two multigene clusters on chromosome 16 (encoding alpha-like globins) and on chromosome 11 (encoding beta-like globins) (Higgs et al., 2012). At each stage of development, the production of alpha-like and beta-like globins is balanced. Beta-globin synthesis is normally controlled by the two beta genes (one on each copy of chromosome 11). In thalassaemia, there are defects in the production of either the alpha-like (alpha-thalassaemia) or the beta-like (beta-thalassaemia) globin chains. The main pathophysiology in beta-thalassaemia results from the synthesis of insufficient beta chains to partner the alpha-globin chains to generate adult haemoglobin (α2β2). Excess alpha chains precipitate in erythroid precursor cells causing dyserthropoiesis, and in mature red blood cells causing membrane damage and haemolysis. If only one of the beta-globin genes bear a mutation, patients suffer from minor microcytic anaemia. If both genes have mutations, this leads to severe microcytic, hypochromic anaemia, which if untreated causes anaemia, splenomegaly, severe bone deformities and death before age 20. Treatment consists of periodic blood transfusion; splenectomy if splenomegaly is present, and treatment of iron overload caused by transfusion. Cure is possible by bone marrow transplantation.
Worldwide about 1.5% of the population are carriers of beta-thalassaemia and these individuals mostly originate from the Mediterranean, Middle East, central Asia, India and southern China, which suggests a selective advantage to carrying such a mutation in these areas. Individuals with either alpha- or beta-thalassaemia trait are somewhat protected in areas where falciparum malaria is or has been endemic, thus explaining the high carrier frequency via natural selection.
For an adult to maintain a normal red blood cell count, about 2–3 million new red blood cells are produced every second. For severe forms of thalassaemia, many erythroblasts and mature red blood cells are damaged, increasing erythropoiesis by 20–30 times.
At a molecular level, haemoglobin synthesis is controlled by two multigene clusters on chromosome 16 (encoding alpha-like globins) and on chromosome 11 (encoding beta-like globins) (Higgs et al., 2012). At each stage of development, the production of alpha-like and beta-like globins is balanced. Beta-globin synthesis is normally controlled by the two beta genes (one on each copy of chromosome 11). In thalassaemia, there are defects in the production of either the alpha-like (alpha-thalassaemia) or the beta-like (beta-thalassaemia) globin chains. The main pathophysiology in beta-thalassaemia results from the synthesis of insufficient beta chains to partner the alpha-globin chains to generate adult haemoglobin (α2β2). Excess alpha chains precipitate in erythroid precursor cells causing dyserthropoiesis, and in mature red blood cells causing membrane damage and haemolysis. If only one of the beta-globin genes bear a mutation, patients suffer from minor microcytic anaemia. If both genes have mutations, this leads to severe microcytic, hypochromic anaemia, which if untreated causes anaemia, splenomegaly, severe bone deformities and death before age 20. Treatment consists of periodic blood transfusion; splenectomy if splenomegaly is present, and treatment of iron overload caused by transfusion. Cure is possible by bone marrow transplantation.
Worldwide about 1.5% of the population are carriers of beta-thalassaemia and these individuals mostly originate from the Mediterranean, Middle East, central Asia, India and southern China, which suggests a selective advantage to carrying such a mutation in these areas. Individuals with either alpha- or beta-thalassaemia trait are somewhat protected in areas where falciparum malaria is or has been endemic, thus explaining the high carrier frequency via natural selection.
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