Haem EMQs

Question 1

A Iron deficiency anaemiaB β-ThalassaemiaC Anaemia of chronic diseaseD Blood lossE AlcoholF Vitamin B12 deficiencyG Renal failureH Aplastic anaemiaI Lead poisoningA 35-year-old man presents to his GP with a 1-month history of increasedtiredness. The patient also admits to diarrhoea and minor abdominal pain duringthis period. His blood tests reveal the following:Hb 9.5 (13–18 g/dL)MCV 64 (76–96 fL)Fe 12.2 (14–31 μmol/L)TIBC 74 (45–66 μmol/L)Ferritin 9.2 (12–200 μg/L)

Answer 1

A Iron deficiency anaemiaIron deficiency anaemia (IDA; A) causes a hypochromic (pallor of thered blood cells on blood film due to reduced Hb synthesis), microcytic(small size) anaemia (low haemoglobin). A reduction in serum iron canbe caused by a number of factors, including inadequate intake, malabsorption(coeliac disease; most likely cause in this case given diarrhoeaand abdominal pain), increased demand (pregnancy) and increasedlosses (bleeding and parasitic infections). Further studies are required todistinguish IDA from other causes of microcytic anaemia: serum ferritinwill be low, while total iron binding capacity (TIBC) and transferrin willbe high.

Question 2

A Iron deficiency anaemiaB β-ThalassaemiaC Anaemia of chronic diseaseD Blood lossE AlcoholF Vitamin B12 deficiencyG Renal failureH Aplastic anaemiaI Lead poisoningA 56-year-old vagrant man presents to the accident and emergency departmentwith weakness in his legs. The patient has a history of poorly controlledCrohn’s disease. His blood tests demonstrate Hb 9.4 (13–18 g/dL) and MCV 121(76–96 fL). A blood film reveals the presence of hypersegmented neutrophils.

Answer 2

F Vitamin B12 deficiencyThe majority of cases of vitamin B12 deficiency (F) occur secondary tomalabsorption: reduced intrinsic factor production due to perniciousanaemia or post-gastrectomy, as well as disease of the terminal ileum.Clinical features will be similar to those of anaemia in mild cases,progressing to neuropsychiatric symptoms and subacute degenerationof the spinal cord (SDSC) in severe cases. Vitamin B12 deficiencyresults in a macrocytic megaloblastic anaemia as a result of inhibitedDNA synthesis (B12 is responsible for the production of thymidine).Hypersegmented neutrophils are pathognomonic of megaloblasticanaemia.

Question 3

A Iron deficiency anaemiaB β-ThalassaemiaC Anaemia of chronic diseaseD Blood lossE AlcoholF Vitamin B12 deficiencyG Renal failureH Aplastic anaemiaI Lead poisoningA 65-year-old man is referred to the haematology department by his GP afterinitially presenting with tiredness, palpitations, petechiae and recent pneumonia.His blood tests reveal Hb 9.8 (13–18 g/dL), MCV 128 (76–96 fL), reticulocytecount 18 (25–100 × 109/L), 1.2 (2–7.5 × 109/L) and platelet count 125(150–400 × 109/L).

Answer 3

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

Question 4

A Iron deficiency anaemiaB β-ThalassaemiaC Anaemia of chronic diseaseD Blood lossE AlcoholF Vitamin B12 deficiencyG Renal failureH Aplastic anaemiaI Lead poisoningA 56-year-old woman presents to her GP with increased tiredness in the pastfew weeks. A past medical history of rheumatoid arthritis is noted. Her bloodtests demonstrate the following:Hb 8.6 (11.5–16 g/dL)MCV 62 (76–96 fL)Fe 10.2 (11–30 μmol/L)TIBC 38 (45–66 μmol/L)Ferritin 220 (12–200 μg/L)

Answer 4

C Anaemia of chronic diseaseAnaemia of chronic disease (ACD; C) occurs in states of chronic infectionand inflammation, for example in tuberculosis (TB), rheumatoidarthritis, inflammatory bowel disease and malignant disease. ACD ismediated by IL-6 produced by macrophages which induces hepcidinproduction by the liver. Hepcidin has the effect of retaining iron inmacrophages (reduced delivery to red blood cells for erythropoiesis) andreduces export from enterocytes (reduced plasma iron levels). Laboratory features of ACD include a microcytic hypochromic anaemia, rouleauxformation (increased plasma proteins), raised ferritin (acute phase protein)as well as reduced serum iron and TIBC.

Question 5

A Iron deficiency anaemiaB β-ThalassaemiaC Anaemia of chronic diseaseD Blood lossE AlcoholF Vitamin B12 deficiencyG Renal failureH Aplastic anaemiaI Lead poisoningA 12-year-old Mediterranean boy presents to his GP with increased tirednessover the past few weeks which is affecting his ability to concentrate at school.Examination is normal. Blood tests demonstrate the following:Hb 9.5 (13–18 g/dL)MCV 69 (76–96 fL)Fe 18.2 (14–31 μmol/L)TIBC 54 (45–66 μmol/L)Ferritin 124 (12–200 μg/L)

Answer 5

B β-Thalassaemiaβ-Thalassaemia (B) is a genetic disorder characterized by the reduced orabsent production of β-chains of haemoglobin. Mutations affecting theβ-globin genes on chromosome 11 lead to a spectrum of clinical featuresdepending on the combinations of chains affected. β-Thalassaemiaminor affects one β-globin chain and is usually asymptomatic, but maypresent with mild features of anaemia. Haematological tests reveal amicrocytic anaemia but iron studies will be normal, differentiating fromiron deficiency anaemia. β-Thalassaemia major occurs due to defectsof both β-globin chains and results in severe anaemia requiring regularblood transfusions, as well as skull bossing and hepatosplenomegaly.

Question 6

A Hereditary sherocytosisB Sickle cell anaemiaC β-ThalassaemiaD Glucose-6-phosphatedehydrogenase deficiencyE Pyruvate kinase deficiencyF Autoimmune haemolytic anaemiaG Haemolytic disease of thenewbornH Paroxysmal nocturnalhaemoglobinuriaI Microangiopathic haemolyticanaemiaA 48-year-old woman diagnosed with chronic lymphocytic leukaemia developsjaundice and on examination is found to have conjunctival pallor. Directantiglobulintest is found to be positive at 37°C.

Answer 6

F Autoimmune haemolytic anaemiaAutoimmune haemolytic anaemia (AIHA; F) is caused by autoantibodiesthat bind to red blood cells (RBCs) leading to splenic destruction. AIHAcan be classified as either ‘warm’ or ‘cold’ depending on the temperatureat which antibodies bind to RBCs. Warm AIHA is IgG mediated,which binds to RBCs at 37°C; causes include lymphoproliferative disorders,drugs (penicillin) and autoimmune diseases (SLE). Cold AIHA isIgM mediated which binds to RBCs at temperatures less than 4°C; thisphenomenon usually occurs after an infection by mycoplasma or EBV.Direct antiglobulin test (DAT) is positive in AIHA and spherocytes areseen on blood film.

Question 7

A Hereditary sherocytosisB Sickle cell anaemiaC β-ThalassaemiaD Glucose-6-phosphatedehydrogenase deficiencyE Pyruvate kinase deficiencyF Autoimmune haemolytic anaemiaG Haemolytic disease of thenewbornH Paroxysmal nocturnalhaemoglobinuriaI Microangiopathic haemolyticanaemiaAn 18-year-old man presents to accident and emergency after eating ameal containing Fava beans. He is evidently jaundiced and has signs suggestiveof anaemia. The patient’s blood film reveals the presence of Heinzbodies.

Answer 7

D Glucose-6-phosphateGlucose-6-phosphate dehydrogenase deficiency (G6PD deficiency; D) iscaused by an X-linked recessive enzyme defect. G6PD is an essentialenzyme in the red blood cell pentose phosphate pathway; the pathway maintains NADPH levels which in turn supply glutathione to neutralizefree radicals that may otherwise cause oxidative damage. Therefore,G6PD deficient patients are at risk of oxidative crises which may beprecipitated by certain drugs (primaquine, sulphonamides and aspirin),fava beans and henna. Attacks result in rapid anaemia, jaundice and ablood film will demonstrate the presence of bite cells and Heinz bodies.

Question 8

A Hereditary sherocytosisB Sickle cell anaemiaC β-ThalassaemiaD Glucose-6-phosphatedehydrogenase deficiencyE Pyruvate kinase deficiencyF Autoimmune haemolytic anaemiaG Haemolytic disease of thenewbornH Paroxysmal nocturnalhaemoglobinuriaI Microangiopathic haemolyticanaemiaA 10-year-old girl presents to accident and emergency with jaundice. Bloodtests reveal uraemia and thrombocytopenia. A peripheral blood film demonstratesthe presence of schistocytes.

Answer 8

I Microangiopathic haemolyticanaemiaMicroangiopathic haemolytic anaemia (I) is caused by the mechanicaldestruction of RBCs in circulation. Causes include thrombotic thrombocytopenicpupura (TTP), haemolytic uraemic syndrome (HUS; E. coliO157:57), disseminated intravascular coagulation (DIC) and systemiclupus erythematosus (SLE). In all underlying causes, the potentiationof coagulation pathways creates a mesh which leads to the intravasculardestruction of RBCs and produces schistocytes (helmet cells).Schistocytes are broken down in the spleen, raising bilirubin levels andinitiating jaundice.

Question 9

A Hereditary sherocytosisB Sickle cell anaemiaC β-ThalassaemiaD Glucose-6-phosphatedehydrogenase deficiencyE Pyruvate kinase deficiencyF Autoimmune haemolytic anaemiaG Haemolytic disease of thenewbornH Paroxysmal nocturnalhaemoglobinuriaI Microangiopathic haemolyticanaemiaA 9-year-old boy from sub-Saharan Africa presents to accident and emergencywith abdominal pain. On examination the child is found to have dactylitis.Blood haemoglobin is found to be 6.2 g/dL and electrophoresis reveals thediagnosis.

Answer 9

B Sickle cell anaemiaSickle cell anaemia (B) is an autosomal recessive genetic haematologicalcondition due to a point mutation in the β-globin chain of haemoglobin(chromosome 11); this mutation causes glumatic acid at position six tobe substituted by valine. Homozygotes for the mutation (HbSS) havesickle cell anaemia while heterozygotes (HbAS) have sickle cell trait.The mutation results in reduced RBC elasticity; RBCs therefore assume asickle shape which leads to the numerous complications associated witha crisis. Blood tests will reveal an anaemia, reticulocytosis and raisedbilirubin. Haemoglobin electrophoresis will distinguish between HbSSand HbAS.

Question 10

A Hereditary sherocytosisB Sickle cell anaemiaC β-ThalassaemiaD Glucose-6-phosphatedehydrogenase deficiencyE Pyruvate kinase deficiencyF Autoimmune haemolytic anaemiaG Haemolytic disease of thenewbornH Paroxysmal nocturnalhaemoglobinuriaI Microangiopathic haemolyticanaemiaA 1-day old baby has developed severe jaundice on the neonatal ward.The mother is rhesus negative and has had one previous pregnancy. Dueto having her first baby abroad, she was not administered prophylacticanti-D.

Answer 10

G Haemolytic disease of thenewbornHaemolytic disease of the newborn (G) occurs when the mother’s blood isrhesus negative and the fetus’ blood is rhesus positive. A first pregnancyor a sensitizing event such as an abortion, miscarriage or antepartumhaemorrhage leads to fetal red blood cells entering the maternal circulationresulting in the formation of anti-D IgG. In a second pregnancy,maternal anti-D IgG will cross the placenta and coat fetal red blood cellswhich are subsequently haemolyzed in the spleen and liver. Therefore,anti-D prophylaxis is given to at-risk mothers; anti-D will coat any fetalred blood cells in the maternal circulation causing them to be removedby the spleen prior to potentially harmful IgG production.

Question 11

A AnisocytosisB Howell–Jolly bodiesC Heinz bodiesD Rouleaux formationE SpherocytesF Target cellsG Cabot ringsH Pappenheimer bodiesI Tear-drop cellsA 34-year-old man, who has a past medical history of splenectomy followingsplenic trauma, presents to his GP with malaise 2 weeks after returning fromabroad. Routine blood results are found to be normal but a blood film demonstratesinclusions within erythrocytes.

Answer 11

B Howell–Jolly bodiesHowell–Jolly bodies (B) are nuclear DNA remnants found in circulatingerythrocytes. On haematoxylin and eosin stained blood film they appearas purple spheres within erythrocytes. In healthy individuals erythrocytesexpel nuclear DNA during the maturation process within thebone marrow; the few erythrocytes containing Howell–Jolly bodies areremoved by the spleen. Common causes of Howell–Jolly bodies includesplenectomy secondary to trauma and autosplenectomy resulting fromsickle cell disease.

Question 12

A AnisocytosisB Howell–Jolly bodiesC Heinz bodiesD Rouleaux formationE SpherocytesF Target cellsG Cabot ringsH Pappenheimer bodiesI Tear-drop cellsA 66-year-old man has a gastroscopy and colonoscopy following a blood testwhich demonstrated a microcytic anaemia. The patient had complained of tirednessand significant weight loss over a 1-month period.

Answer 12

A AnisocytosisAnisocytosis (A) is defined as the variation in the size of circulatingerythrocytes. The most common cause is iron deficiency anaemia (IDA),but thalassaemia, megaloblastic anaemia and sideroblastic anaemia areall causative. As well as blood film analysis, anisocytosis may be detectedas a raised red cell distribution width (RDW), a measure of variationin size of red blood cells. In the case of IDA, anisocytosis results due todeficient iron supply to produce haemoglobin.

Question 13

A AnisocytosisB Howell–Jolly bodiesC Heinz bodiesD Rouleaux formationE SpherocytesF Target cellsG Cabot ringsH Pappenheimer bodiesI Tear-drop cellsA 36-year-old woman presents to her GP after a 1-month history of tirednessand recurrent chest infections. Blood tests reveal a pancytopenia and a subsequentbone marrow aspirate reveals a dry tap.

Answer 13

I Tear-drop cellsTear-drop cells (I), also known as dacrocytes, are caused by myelofibrosis.The pathogenesis of myelofibrosis is defined by the bone marrowundergoing fibrosis, usually following a myeloproliferative disordersuch as polycythaemia rubra vera or essential thrombocytosis. Bonemarrow production of blood cells decreases resulting in a pancytopenia.The body compensates with extra-medullary haemopoiesis causinghepatosplenomegaly. Blood film will demonstrate leuko-erythroblasts,tear-drop cells and circulating megakaryocytes. Bone marrow aspirate isdescribed as a ‘dry and bloody’ tap.

Question 14

A AnisocytosisB Howell–Jolly bodiesC Heinz bodiesD Rouleaux formationE SpherocytesF Target cellsG Cabot ringsH Pappenheimer bodiesI Tear-drop cellsA 3-week-old neonate is found to have prolonged jaundice with serious risk ofkernicterus. Blood film demonstrates the presence of ‘bite cells’ as well as inclusionswithin erythrocytes.

Answer 14

C Heinz bodiesHeinz bodies (C) are inclusion bodies found within erythrocytes thatrepresent denatured haemoglobin as a result of reactive oxygen species.Heinz bodies are most commonly caused by erythrocyte enzyme deficienciessuch as glucose-6-phosphate dehydrogenase (G6PD) deficiency,which may present in neonates with prolonged jaundice and NADPHdeficiency (leading to accumulation of hydrogen peroxide), as wellas chronic liver disease and α-thalassaemia. Damaged erythrocytes areremoved in the spleen by macrophages leading to the formation of ‘bitecells’.

Question 15

A AnisocytosisB Howell–Jolly bodiesC Heinz bodiesD Rouleaux formationE SpherocytesF Target cellsG Cabot ringsH Pappenheimer bodiesI Tear-drop cellsA 45-year-old woman with known Graves’ diseases presents to her GP withincreased tiredness. She is found to have a megaloblastic anaemia.

Answer 15

G Cabot ringsCabot rings (G) are looped structures found within erythrocytes whichmay be caused by megaloblastic anaemia, i.e. inhibition of erythrocyteproduction occurring as a result of reduced DNA synthesis secondary to vitamin B12 deficiency. Vitamin B12 deficiency is most commonly causedby intrinsic factor (a protein required for vitamin B12 absorption) deficiencyas a result of pernicious anaemia. Pernicious anaemia is causedby antibody destruction of gastric parietal cells which produce intrinsicfactor and may be associated with other autoimmune diseases.

Question 16

A Immune thrombocytopenicpurpuraB Idiopathic thromboticthrombocytopenic purpuraC Disseminated intravascularcoagulationD Glanzmann’s thrombastheniaE Von Willebrand diseaseF Haemophilia AG Haemophilia BH Hereditary haemorrhagictelangiectasiaI Bernard–Soulier syndromeA 4-year-old girl is seen by her GP due to recent onset petechiae on her feetand bleeding of her gums when she brushes her teeth. The child’s platelet countis found to be 12 500 per μL. The GP prescribes prednisolone and reassures thechild’s mother that the bleeding will resolve.

Answer 16

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

Question 17

A Immune thrombocytopenicpurpuraB Idiopathic thromboticthrombocytopenic purpuraC Disseminated intravascularcoagulationD Glanzmann’s thrombastheniaE Von Willebrand diseaseF Haemophilia AG Haemophilia BH Hereditary haemorrhagictelangiectasiaI Bernard–Soulier syndromeA 28-year-old man attends the haematology outpatient clinic regarding a longstandingcondition he has suffered from. His disorder is related to a deficiencyin factor 8 and therefore requires regular transfusions to replace this clottingfactor.

Answer 17

F Haemophilia AHaemophilia A (F) is an X-linked genetic disorder and hence onlyaffects men. Haemophilia A is characterized by a deficiency in factor 8.Haemophilia A is diagnosed by a reduced APTT as well as reducedfactor8. Symptoms depend on severity of disease: mild disease featuresbleeding after surgery/trauma; moderate disease results in bleedingafter minor trauma; severe disease causes frequent spontaneous bleeds.Clinical features include haemarthrosis (causing fixed joints) and musclehaematoma (causing atrophy and short tendons).

Question 18

A Immune thrombocytopenicpurpuraB Idiopathic thromboticthrombocytopenic purpuraC Disseminated intravascularcoagulationD Glanzmann’s thrombastheniaE Von Willebrand diseaseF Haemophilia AG Haemophilia BH Hereditary haemorrhagictelangiectasiaI Bernard–Soulier syndromeA 34-year-old man is taken to the local accident and emergency after sufferingan episode of jaundice, fever and worsening headache. Blood tests reveal a lowplatelet count and blood film is suggestive of a microangiopathic haemolyticanaemia picture.

Answer 18

B Idiopathic thromboticthrombocytopenic purpuraIdiopathic thrombotic thrombocytopenic purpura (B) occurs due toplatelet microthrombi. Presenting features include microangiopathichaemolytic anaemia (red blood cells coming into contact with microscopicclots are damaged by shear stress), renal failure, thrombocytopenia,fever and neurological signs (hallucinations/stroke/headache). Amutation in the ADAM-ST13 gene, coding for a protease that cleavesvon Willebrand factor (vWF) allows for the formation of vWF multimersenabling platelet thrombi to form causing organ damage.

Question 19

A Immune thrombocytopenicpurpuraB Idiopathic thromboticthrombocytopenic purpuraC Disseminated intravascularcoagulationD Glanzmann’s thrombastheniaE Von Willebrand diseaseF Haemophilia AG Haemophilia BH Hereditary haemorrhagictelangiectasiaI Bernard–Soulier syndromeA 68-year-old man on the Care of the Elderly ward is confirmed to have Gramnegativesepsis. The patient is bleeding from his mouth and is in shock. Initialblood tests reveal a reduced platelet count, anaemia and renal failure.

Answer 19

C Disseminated intravascularcoagulationDisseminated intravascular coagulation (DIC; C) may be caused byGram-negative sepsis, malignancy, trauma, placental abruption oramniotic fluid embolus. Tissue factor is released which triggers theactivation of the clotting cascade, leading to platelet activation(thrombosis in microcirculation) and fibrin deposition (haemolysis).The consumption of platelets and clotting factors predisposes tobleeding. Plasmin is also generated in DIC which causes fibrinolysis,perpetuating the bleeding risk. The clinical manifestations ofDIC are therefore linked to microthombus production (renal failureand neurological signs) and reduced platelets, clotting factorsand increased fibrinolysis (bruising, gastrointestinal bleeding andshock).

Question 20

A Immune thrombocytopenicpurpuraB Idiopathic thromboticthrombocytopenic purpuraC Disseminated intravascularcoagulationD Glanzmann’s thrombastheniaE Von Willebrand diseaseF Haemophilia AG Haemophilia BH Hereditary haemorrhagictelangiectasiaI Bernard–Soulier syndromeA 2-year-old boy is taken to see the GP due to his mother noticing bruisingon his arms and legs after playing in the park. The parent mentions that shehas also noticed several recent nose bleeds in her son but thought he would‘grow out of it’. Investigations reveal a low APTT, low factor 8 levels and lowRistocetein cofactor activity.

Answer 20

E Von Willebrand diseasevon Willebrand disease (vWD; E) is an autosomal dominant conditioncaused by a mutation on chromosome 12. Physiologically, vonWillebrand factor (vWF) has two roles: platelet adhesion and factor 8production. Therefore, in vWD, where there is a deficiency in vWF,there is a defect in platelet plug formation as well as low levels of factor8. Clinically, patients will present with gum bleeding, epistaxis orprolonged bleeding after surgery. Investigations will reveal a high/normal APTT, low factor 8 levels, low ristocetin cofactor activity, poorristocetin aggregation and normal PTT,

Question 21

A Factor V LeidenB Antiphospholipid syndromeC MalignancyD Protein S deficiencyE Antithrombin deficiencyF Prothrombin G20210A mutationG Oral contraceptive pillH Buerger’s diseaseI Chronic liver diseaseA 35-year-old Caucasian man presents to accident and emergency with deeppain and swelling in his left calf. His past medical history reveals history ofrecurrent DVTs. The patient’s notes reveal a letter from his haematologist whohad diagnosed a condition caused by a substitution mutation.

Answer 21

F Prothrombin G20210A mutationProthrombin G20210A (F) is an inherited thrombophilia caused by thesubstitution of guanine with adenine at the 20210 position of the prothrombingene. Physiologically, prothrombin promotes clotting aftera blood vessel has been damaged. The G20210A causes the amplificationof prothrombin production thereby increasing the risk of clotting,and causing a predisposition to deep vein thrombosis and pulmonary embolism.The prevalence of the mutation is approximately 5 per centin the Caucasian population, the race with the greatest preponderance.

Question 22

A Factor V LeidenB Antiphospholipid syndromeC MalignancyD Protein S deficiencyE Antithrombin deficiencyF Prothrombin G20210A mutationG Oral contraceptive pillH Buerger’s diseaseI Chronic liver diseaseA 38-year-old woman presents to accident and emergency with abdominalpain as well as passing blood and tissue per vagina. Ectopic pregnancyis diagnosed after ultrasound. The patient’s past medical history includes ahaematologicalcondition in which a clotting factor is unable to be degradedby activated protein C.

Answer 22

A Factor V LeidenFactor V Leiden (A) is an autosomal dominant inherited thrombophilia.Under normal circumstances protein C inhibits factor 5. In Factor VLeiden a mutation of the F5 gene that codes for factor 5, whereby anarginine codon is substituted for a glutamine codon, results in impaireddegradation of factor 5 by protein C. As a result, patients are at risk ofdeep vein thrombosis and miscarriage. Diagnostic tests determine thefunctionality of activated protein C.

Question 23

A Factor V LeidenB Antiphospholipid syndromeC MalignancyD Protein S deficiencyE Antithrombin deficiencyF Prothrombin G20210A mutationG Oral contraceptive pillH Buerger’s diseaseI Chronic liver diseaseA 32-year-old woman is seen by her rheumatologist to follow up her longstandingsystemic lupus erythematosus (SLE). The patient has a history ofrecurrentmiscarriages. The woman is positive for anti-cardiolipin antibodies andlupus anticoagulant.

Answer 23

B Antiphospholipid syndromeAntiphospholipid syndrome (APLS; B) is an autoimmune disorder thatmay present with stroke (arterial thrombosis), deep vein thrombosis(venous thrombosis) and/or recurrent miscarriages. APLS may be primary(not associated with autoimmune disease) or secondary to autoimmunedisease such as SLE. Anti-cardiolipin antibodies and lupusanticoagulant bind to phospholipids on cell surface membranes of cellscausing the activation of the coagulation cascade and thereby promotingclot formation. Diagnosis involves demonstrating the presence ofcirculating anti-cardiolipin antibodies and lupus anticoagulant.

Question 24

A Factor V LeidenB Antiphospholipid syndromeC MalignancyD Protein S deficiencyE Antithrombin deficiencyF Prothrombin G20210A mutationG Oral contraceptive pillH Buerger’s diseaseI Chronic liver diseaseA 45-year-old man, who has a 50 pack/year history of smoking, is referred tothe vascular outpatient clinic by his GP after suffering intermittent claudication.A diagnostic angiogram reveals a corkscrew appearance of his lowerlimb arteries.

Answer 24

H Buerger’s diseaseBuerger’s disease (thromboangitis obliterans; H) is a vasculitis of small/medium arteries and veins of the hands and feet; it is strongly relatedto smoking. Claudication may be the initial presentation but as thedisease progresses there is an association with recurrent arterial andvenous thrombosis leading to gangrene and amputation in severe cases.Angiograms of the upper and lower limbs are helpful in the diagnosis ofBuerger’s disease; a corkscrew appearance of the arteries may arise dueto persistent vascular damage.

Question 25

A Factor V LeidenB Antiphospholipid syndromeC MalignancyD Protein S deficiencyE Antithrombin deficiencyF Prothrombin G20210A mutationG Oral contraceptive pillH Buerger’s diseaseI Chronic liver diseaseA 37-year-old man presents to accident and emergency with shortness ofbreath and severe pleuritic chest pain. A CTPA reveals the diagnosis of pulmonaryembolism. The patient’s haematological records state the patient has acondition that leads to the persistence of factors 5a and 8a causing increasedrisk of venous thrombosis.

Answer 25

D Protein S deficiencyProtein S deficiency (D) is associated with the impaired degradation offactors Va and VIIIa. Protein S and protein C are physiological anticoagulants.Deficiency of protein S leads to persistence of factors 5a and8a in the circulation and hence patients have a susceptibility to venousthrombosis. Three types of protein S deficiency exist: type I (quantitativedefect) and types II and III (qualitative defect). Since protein S is avitamin K dependent anticoagulant, warfarin treatment and liver diseasemay also lead to venous thrombosis in rare cases (the majority of casesshow increased bleeding).

Question 26

A Immediate haemolytic transfusionreactionB Febrile non-haemolytic reactionC Iron overloadD IgA deficiencyE Transfusion related lung injuryF Bacterial infectionG Delayed haemolytic transfusionreactionH Fluid overloadI Graft versus host diseaseAn 82-year-old man has just received a blood transfusion following a low haemoglobinlevel on the Care of the Elderly ward. He is now short of breath and iscoughing up pink frothy sputum.

Answer 26

H Fluid overloadFluid overload (H) is an immediate complication of blood transfusion.Clinical features suggestive of fluid overload will include dyspnoea,distended neck veins and pink frothy sputum. Usually fluid overloadoccurs in situations where the blood transfusion rate is too fast; atransfusion would generally have to run at more than 2 mL/kg/hour toinduce fluid overload. Patients with pre-existing cardiac or renal failureare prone to fluid overload as a result of blood transfusion.

Question 27

A Immediate haemolytic transfusionreactionB Febrile non-haemolytic reactionC Iron overloadD IgA deficiencyE Transfusion related lung injuryF Bacterial infectionG Delayed haemolytic transfusionreactionH Fluid overloadI Graft versus host diseaseA 34-year-old HIV-positive man receives a regular blood transfusion as part ofhis beta-thalassaemia major treatment regimen. He soon develops diarrhoeaand a maculopapular rash on his limbs.

Answer 27

I Graft versus host diseaseGraft versus host disease (GVHD; I) occurs due to the transfer of donorlymphocytes to the recipient in a blood transfusion in patients who areimmunosuppressed. Normally, the immune system is strong enough todetect and destroy donor lymphocytes. However, in immunosuppression(stem cell transplant patients/chemotherapy/malignancy/HIV) the donorlymphocytes cannot be destroyed; these foreign lymphocytes persistand target host tissue, especially the gastrointestinal tract and skin.Symptoms of GVHD include diarrhoea, maculopapular rash and skinnecrosis. To minimize GVHD, donor blood is irradiated to removelymphocytes.

Question 28

A Immediate haemolytic transfusionreactionB Febrile non-haemolytic reactionC Iron overloadD IgA deficiencyE Transfusion related lung injuryF Bacterial infectionG Delayed haemolytic transfusionreactionH Fluid overloadI Graft versus host diseaseA 34-year-old man requires a blood transfusion following a road traffic accident.However, soon after the transfusion, the patient is dyspnoeic and hypotensive.Investigation into the patient’s past medical history reveals a history ofrecurrent chest and gastrointestinal infections.

Answer 28

D IgA deficiencyIgA deficiency (D) leads to recurrent mild infections of the mucousmembranes lining the airways and digestive tract. In affected patientsserum IgA levels are undetectable but IgG and IgM levels are normal.IgA is found in mucous secretions from the respiratory and gastrointestinaltracts and plays a key role in mucosal immunity. IgA deficientpatients are also predisposed to severe anaphylactic reactions to bloodtransfusions due to the presence of IgA in donor blood.

Question 29

A Immediate haemolytic transfusionreactionB Febrile non-haemolytic reactionC Iron overloadD IgA deficiencyE Transfusion related lung injuryF Bacterial infectionG Delayed haemolytic transfusionreactionH Fluid overloadI Graft versus host diseaseA 56-year-old man is given a blood transfusion following severe blood lossafter a hip replacement operation. Three hours after the transfusion, the patientdevelops shortness of breath, a dry cough and a fever of 39°C.

Answer 29

E Transfusion related lung injuryTransfusion-related lung injury (TRALI; E) is characterized by acutenon-cardiogenic pulmonary oedema that occurs within 6 hours followingblood transfusion. The pathogenesis of TRALI involves the presenceof anti-white blood cell antibodies in the donor blood that attack hostleukocytes; sensitizing events in donors include previous blood transfusionor transplantation. Clinical features of TRALI are dry cough, dyspnoeaand fever.

Question 30

A Immediate haemolytic transfusionreactionB Febrile non-haemolytic reactionC Iron overloadD IgA deficiencyE Transfusion related lung injuryF Bacterial infectionG Delayed haemolytic transfusionreactionH Fluid overloadI Graft versus host diseaseA 29-year-old woman requires an immediate blood transfusion after sufferinga post-partum haemorrhage. However, 30 minutes after her transfusion shedevelops abdominal pain, facial flushing and vomiting. Analysis of the woman’surine reveals the presence of haemoglobin.

Answer 30

A Immediate haemolytic transfusionreactionImmediate haemolytic transfusion reaction (IHTR; A) is characterizedby ABO incompatibility and occurs 1–2 hours post-transfusion. Clinicalfeatures include abdominal pain, loin pain, facial flushing, vomiting andhaemoglobinuria. Host IgG and IgM target donor red blood cells which aresubsequently removed by the reticuloendothelial system. The most severereaction occurs if a group O patient is transfused with group A blood.

Question 31

A Acute lymphoblastic leukaemiaB Acute promyelocytic leukaemiaC Chronic myeloid leukaemiaD Chronic lymphocytic leukaemiaE Hairy cell leukaemiaF T-cell prolymphocytic leukaemiaG Large granular lymphocyticleukaemiaH Adult T-cell leukaemiaI Acute myeloid leukaemiaA 62-year-old woman is seen by a GP due to a recent chest infection that hasbeen troubling her. Initial blood tests show an elevated white cell count withspecifically raised granulocytes. Following referral to a haematologist, a bonemarrow biopsy reveals a hypercellular bone marrow and cytogenetic screeningsuggests a translocation between chromosomes 9 and 22.

Answer 31

C Chronic myeloid leukaemiaChronic myeloid leukaemia (CML; C) is most prevalent in the elderlypopulation and is commonly suspected secondary to routine blood tests.Blood results will show an elevated level of granulocytes (neutrophils,basophils and eosinophils). Blood film will demonstrate myeloid cellsat different stages of maturation. Bone marrow biopsy in CML patientssuggests hypercellularity. Ninety-five per cent of cases are caused bythe Philadelphia chromosome, a chromosomal translocation betweenchromosomes 9 and 22; this results in the BCR-Abl fusion oncogenethat has tyrosine kinase activity. Recent novel therapies for CML includeimatinib, a BCR-Abl inhibitor.

Question 32

A Acute lymphoblastic leukaemiaB Acute promyelocytic leukaemiaC Chronic myeloid leukaemiaD Chronic lymphocytic leukaemiaE Hairy cell leukaemiaF T-cell prolymphocytic leukaemiaG Large granular lymphocyticleukaemiaH Adult T-cell leukaemiaI Acute myeloid leukaemiaA 41-year-old man is referred to a haematologist by his general practitionerafter several recent chest infections and tiredness. On examination, bruisesare seen on his lower limbs as well as splenomegaly. Initial blood tests reveal apancytopenia. Further testing demonstrates the presence of tumour cells thatexpress tartrate-resistant acid phosphatase.

Answer 32

E Hairy cell leukaemiaHairy cell leukaemia (HCL; E) is a haematological malignancy ofB lymphocytes and a subtype of chronic lymphocytic leukaemia. Itmost commonly occurs in middle-aged men. The cancer derives itsname from the fine hair-like projections that are seen on tumour cellson microscopy. Cell surface markers include CD25 (IL-2 receptor) andCD11c (adhesion molecule). Diagnosis can be confirmed by the presenceof tartrate-resistant acid phosphatase (TRAP) on cytochemical analysis.Clinical features relate to invasion of the spleen (splenomegaly), liver(hepatomegaly) and bone marrow (pancytopenia).

Question 33

A Acute lymphoblastic leukaemiaB Acute promyelocytic leukaemiaC Chronic myeloid leukaemiaD Chronic lymphocytic leukaemiaE Hairy cell leukaemiaF T-cell prolymphocytic leukaemiaG Large granular lymphocyticleukaemiaH Adult T-cell leukaemiaI Acute myeloid leukaemiaA 60-year-old man presents to his GP with fever, malaise and cough. On examination,the man is found to have petechiae on his legs as well as gum hypertrophy.Blood tests reveal anaemia, leukocytopenia and thrombocytopenia. A bloodfilm demonstrates the presence of Auer rods within blast cells.

Answer 33

I Acute myeloid leukaemiaAcute myeloid leukaemia (AML; I) is characterized by more than 20 percent myleoblasts in the bone marrow. AML also causes proliferationof megakaryocytes and erythrocytes. Mutations that can cause AMLinclude internal tandem duplications of the FLT3 gene (coding for atyrosine kinase) and t(8;21) (a translocation causing a compressor complexto inhibit haematopoietic differentiation. Primary causes includeDown’s syndrome; secondary causes include myeloproliferative disease. Blood tests will reveal a variable white cell count, anaemia,thrombocytopenia and reduced neutrophil count. Auer rods on bloodfilm are pathognomonic, which will also be leuko-erythroblastic.Immunophenotyping of CD13, CD33 or CD34 can also aid diagnosis.

Question 34

A Acute lymphoblastic leukaemiaB Acute promyelocytic leukaemiaC Chronic myeloid leukaemiaD Chronic lymphocytic leukaemiaE Hairy cell leukaemiaF T-cell prolymphocytic leukaemiaG Large granular lymphocyticleukaemiaH Adult T-cell leukaemiaI Acute myeloid leukaemiaA 42-year-old Japanese migrant presents to his GP with generalized lymphadenopathyand nodules on his arms. On examination the patient has hepatosplenomegaly.Blood tests reveal lymphocytosis and a raised calcium level.

Answer 34

H Adult T-cell leukaemiaAdult T-cell leukaemia (adult T-cell lymphoma; ATL; H) is a rare haematologicalmalignancy with poor prognosis. It is caused by human T-cellleukaemia virus type 1 (HTLV-1), endemic in Japan and the Caribbean.Tumour cells express the cell surface protein CD4 and will contain theHTLV-1 virus within; the nuclei of ATL cells have a characteristic cloverleafappearance. Clinical features include lymphadenopathy, hepatosplenomegaly,skin lesions and hypercalcaemia.

Question 35

A Acute lymphoblastic leukaemiaB Acute promyelocytic leukaemiaC Chronic myeloid leukaemiaD Chronic lymphocytic leukaemiaE Hairy cell leukaemiaF T-cell prolymphocytic leukaemiaG Large granular lymphocyticleukaemiaH Adult T-cell leukaemiaI Acute myeloid leukaemiaA 70-year-old man is reviewed by his GP after having felt tired and experiencedweight loss over a 2-month period. The patient has lymphadenopathy onexamination. Blood tests demonstrates a lymphocytosis of 4500 cells per microlitreand smudge cells can be visualized on a peripheral blood film.

Answer 35

D Chronic lymphocytic leukaemiaChronic lymphocytic leukaemia (CLL; D) is a B-cell neoplasm characterizedby a lymphocyte count of over 4000 cells per microlitre. CLLmost commonly occurs in elderly men. The cancer presents primarilyin the lymph nodes with small lymphocytes containing irregular nucleimixed with larger prolymphocytes. Prolymphocytes may aggregate toform pathognomonic proliferation centres. Blood film may reveal thepresence of smudge cells. Clinical features are non-specific and includetiredness and weight loss. Hypogammaglobulinaemia is an associatedimmune phenomenon. CLL may convert into more aggressive formsincluding prolymphocytic transformation and diffuse-large B-cell lymphoma(Richter’s syndrome).

Question 36

A Diffuse large B-cell lymphomaB Burkitt lymphomaC Follicular lymphomaD Small lymphocytic leukaemiaE Mantle cell lymphomaF Peripheral T-cell lymphomaG Mycosis fungoidesH Angiocentric lymphomaI Hodgkin’s lymphomaA 5-year-old boy is seen by a volunteer doctor at an Ethiopian refugee camp.On examination the child has a prominent swelling on the left side of his jaw.A tissue sample of the mass demonstrates a ‘starry sky’ appearance on lightmicroscopy.

Answer 36

B Burkitt lymphomaBurkitt lymphoma (BL; B) is a haematological cancer of B lymphocytescaused by latent Epstein–Barr viral (EBV) infection and is most prevalentin Africa, affecting children and teenagers. Subtypes of BL includeendemic, sporadic and immunodeficiency-associated disease. EndemicBL presents with a mandibular mass whereas non-endemic types present with an abdominal mass. All forms are highly associated with translocationsof the c-myc gene on chromosome 8 (the most common with theIg heavy chain on chromosome 14). A ‘starry sky’ appearance is characteristicwhen viewing BL cells under microscopy.

Question 37

A Diffuse large B-cell lymphomaB Burkitt lymphomaC Follicular lymphomaD Small lymphocytic leukaemiaE Mantle cell lymphomaF Peripheral T-cell lymphomaG Mycosis fungoidesH Angiocentric lymphomaI Hodgkin’s lymphomaA 52-year-old man presents to his GP with painless lymphadenopathy which hedescribes as having fluctuated in size over the past month, as well as experiencingnight sweats and weight loss. He also mentions the lumps become painfulwhen he drinks alcohol. Further biopsy of the lumps reveals the presence ofReed–Sternberg cells.

Answer 37

I Hodgkin’s lymphomaHodgkin’s lymphoma (I) results from the proliferation of B cells fromthe germinal centre. The pathogenesis is linked to EBV infection whichactivates NF-κB, preventing apoptosis of infected cells. Release of IL-5from B-cells activates eosinophils, prolonging the life of B cells further.Histologically, Hodgkin’s lymphoma is characterized by the presenceof Reed–Sternberg cells (binucleate/multinucleate cells with abundantcytoplasm, inclusion-like nucleoli and surrounded by eosinophils).Lymphadenopathy associated with Hodgkin’s lymphoma is usually painless,asymmetrical, fluctuates in size and is painful with alcohol intake.Other clinical features include fever, night sweats, weight loss and Pel–Ebstein fever (intermittent fever every 2 weeks). Unlike non-Hodgkin’slymphoma, extra-nodal involvement is rare.

Question 38

A Diffuse large B-cell lymphomaB Burkitt lymphomaC Follicular lymphomaD Small lymphocytic leukaemiaE Mantle cell lymphomaF Peripheral T-cell lymphomaG Mycosis fungoidesH Angiocentric lymphomaI Hodgkin’s lymphomaA 60-year-old man presents to his GP with malaise, night sweats and weightloss. On examination the patient is found to have generalized lymphadenopathyand hepatomegaly. Cytogenetic investigation a few weeks later by a haematologistreveals a translocation between chromosomes 11 and 14, which has causedoverexpression of the BCL-2 protein.

Answer 38

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

Question 39

A Diffuse large B-cell lymphomaB Burkitt lymphomaC Follicular lymphomaD Small lymphocytic leukaemiaE Mantle cell lymphomaF Peripheral T-cell lymphomaG Mycosis fungoidesH Angiocentric lymphomaI Hodgkin’s lymphomaA 40-year-old woman is referred to a haematologist after she is found to havegeneralized, painless lymphadenopathy. A report on tumour cell morphologystates the presence of both centrocytes and centroblasts.

Answer 39

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

Question 40

A Diffuse large B-cell lymphomaB Burkitt lymphomaC Follicular lymphomaD Small lymphocytic leukaemiaE Mantle cell lymphomaF Peripheral T-cell lymphomaG Mycosis fungoidesH Angiocentric lymphomaI Hodgkin’s lymphomaA 62-year-old HIV-positive man presents to a haematologist with a 3-monthhistory of weight loss and tiredness. On examination, the patient has a mass onhis neck which the patient states has been rapidly growing. Staining of biopsytissue demonstrates the present of large B cells which are positive for EBV.

Answer 40

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

Question 41

A Essential thrombocythaemiaB MyelofibrosisC Chronic myelo-monocyticleukaemiaD Refractory anaemia with excessblastsE Polycythaemia rubraveraF Refractory anaemia with ringedsideroblastsG Refractory anaemiaH 5q-SyndromeI Multiple myelomaA 40-year-old man is referred to a haematologist after suffering an episodeof petechiae on his legs followed by a burning sensation in his fingers anddeep vein thrombosis a few weeks later. Blood tests reveal a platelet count of850 × 109/L.

Answer 41

A Essential thrombocythaemiaEssential thrombocythaemia (A) results in a high platelet count, whichquickly become dysfunctional; it is characterized by periods of bleedingor thrombosis. Clinical features of bleeding events include gastrointestinalbleeding, bruising, petechiae and/or menorrhagia. Thrombotic eventsmanifest as erythromelalgia (erythema, swelling, pain and/or burningsensation in the extremities), digital ischaemia, cerebrovascular accident,deep vein thrombosis and Budd–Chiari syndrome. Blood tests will demonstratea platelet count of over 600 × 109/L and the bone marrow willbe hypercellular with giant platelets, as well as megakaryocyte clusteringand hyperplasia. Treatment options include hydroxyurea or anagrelide.

Question 42

A Essential thrombocythaemiaB MyelofibrosisC Chronic myelo-monocyticleukaemiaD Refractory anaemia with excessblastsE Polycythaemia rubraveraF Refractory anaemia with ringedsideroblastsG Refractory anaemiaH 5q-SyndromeI Multiple myelomaA 52-year-old woman presents to her GP due to increased tiredness. The patientalso reports easy bruising and numerous bouts of pneumonia which haveoccurred over the past 6 months. On examination, the patient has splenomegaly.Blood tests reveal a low white cell and platelet count. Blood film reveals the presenceof tear drop cells and on bone marrow aspiration there is a ‘dry’ tap.

Answer 42

B MyelofibrosisIn myelofibrosis (B) the bone marrow undergoes fibrosis, the cause of whichis unknown. The body compensates with extra-medullary haemopoiesiscausing enlargement of the spleen and liver. The underlying pathogenesisis related to abnormal megakaryocytes releasing PDGF and TGF-β whichstimulate fibroblast proliferation. Blood tests will show an initial rise inwhite cell and platelet counts during the compensatory phase; as fibrosisprogresses the bone marrow reduces white cell and platelet production.Blood film will be leukoerythroblastic, with tear-drop cells and circulatingmegakaryocytes (fibrosis causes ejection of megakaryocytes from the bonemarrow). Bone marrow aspirate will demonstrate a ‘dry’ or bloody tap.

Question 43

A Essential thrombocythaemiaB MyelofibrosisC Chronic myelo-monocyticleukaemiaD Refractory anaemia with excessblastsE Polycythaemia rubraveraF Refractory anaemia with ringedsideroblastsG Refractory anaemiaH 5q-SyndromeI Multiple myelomaA 60-year-old man is referred to a haematologist after complaining of backpain and tiredness as well as recent onset low mood. Urine tests reveal the presenceof Bence–Jones proteins. An X-ray of the patient’s spine shows the presenceof lytic lesions.

Answer 43

I Multiple myelomaMultiple myeloma (I) is defined as the proliferation of plasma cells inthe bone marrow (>10 per cent plasma cells). Myeloma cells releasemonoclonal antibodies (most commonly IgG or IgA) and/or light chains(paraproteins); IgA production significantly increases the viscosity ofthe blood. Diagnosis is based on paraprotein bands of greater than30 g/L on electrophoresis. Blood tests will demonstrate an increased ESR and calcium levels as well as rouleaux formation on blood film.Bence–Jones proteins (immunoglobulin light chains) may be present inthe urine. Plasma cells visualized from bone marrow biopsy are atypical,with multiple nuclei, prominent nucleoli and cytoplasmic granules (containingimmunoglobulin). X-rays may reveal punched-out lytic lesions.

Question 44

A Essential thrombocythaemiaB MyelofibrosisC Chronic myelo-monocyticleukaemiaD Refractory anaemia with excessblastsE Polycythaemia rubraveraF Refractory anaemia with ringedsideroblastsG Refractory anaemiaH 5q-SyndromeI Multiple myelomaA 72-year-old man presents with a 1-month history of fever, night sweats andweight loss. Blood tests reveal a monocyte count of 1400/mm3 in the peripheralblood and a bone marrow biopsy demonstrates that myeloblasts constitute 16per cent of his bone marrow

Answer 44

C Chronic myelo-monocyticChronic myelo-monocytic leukaemia (CMML; C) is a myelodysplastic/myeloproliferative disease which most commonly affects the elderlypopulation, defined by a monocytosis of >1000/mm3 and increasednumber of monocytes in the bone marrow. Myeloblasts make up

Question 45

A Essential thrombocythaemiaB MyelofibrosisC Chronic myelo-monocyticleukaemiaD Refractory anaemia with excessblastsE Polycythaemia rubraveraF Refractory anaemia with ringedsideroblastsG Refractory anaemiaH 5q-SyndromeI Multiple myelomaA 43-year-old woman presents to her general practitioner with headaches, episodesof dizziness and a strange itching sensation after she comes out of thebath. On examination a plethoric appearance is noted. Blood tests reveal a haemoglobinof 19 g/dL and erythropoietin levels are suppressed.

Answer 45

E Polycythaemia rubraveraPolycythaemia rubra vera (PRV; E) is characterized by proliferation oferythroid, granulocytic and megakaryocyte lines. Many PRV cases are dueto a V167F mutation on exon 2 of the JAK2 gene, leading to uncontrolledstem cell proliferation. Clinical features include hyperviscosity (headaches,dizziness and stroke), hyper-mast-cell degranulation (pruritis after hotbaths, plethoric skin and peptic ulceration) and increased cell turnover(gout). Blood tests will reveal a haemoglobin concentration above 18 g/dL,leukocytosis and thrombocytosis. Erythropoietin levels are low due to anegative-feedback response from increased erythrocyte production.

Question 46

A Temporal arteritisB Renal cell carcinomaC Colorectal cancerD Rheumatoid arthritisE Miliary tuberculosisF Acute pancreatitisG SchistosomiasisH SarcoidosisI Epstein–Barr infectionA 56-year-old woman visits her GP for a regular check-up for a chronic conditionshe suffers from. On examination, she has signs of long-term steroidtherapy. There is ulnar deviation at her metacarpophalangeal joints. Bloodtests reveal a microcytic hypochromic anaemia, low iron and total iron bindingcapacity, but a raised ferritin level.

Answer 46

D Rheumatoid arthritisRheumatoid arthritis (RA; D) is an inflammatory disease that mainlyaffects the small joints of the hands but systemic involvement can bea feature, manifesting in the lungs (fibrosis), heart (pericarditis) and eyes (scleritis). RA is a cause of anaemia of chronic disease (ACD),which is mediated by IL-6 produced by macrophages. IL-6 induceshepcidin production by the liver which has the effect of retaining ironin macrophages (reduced delivery to red blood cells for erythropoiesis)and decreases export from enterocytes (reduced plasma iron levels).Laboratory features of ACD include a microcytic hypochromic anaemia,rouleaux formation and raised ferritin (acute phase protein).

Question 47

A Temporal arteritisB Renal cell carcinomaC Colorectal cancerD Rheumatoid arthritisE Miliary tuberculosisF Acute pancreatitisG SchistosomiasisH SarcoidosisI Epstein–Barr infectionA 45-year-old man presents to accident and emergency with an excruciatingheadache. Blood tests show an erythrocyte sedimentation rate of 110 mm/hour.

Answer 47

A Temporal arteritisTemporal arteritis (A) is a vasculitis most commonly affecting the mediumand large arteries of the head. It is also known as giant cell arteritisdue to the inflammatory cells that are visualized on biopsy. Prominenttemporal arteries with regional tenderness, coupled with an erythrocytesedimentation rate (ESR) of more than 60 mm/hour is highly suggestiveof temporal arteritis. ESR may be raised due to increase plasma proteins(fibrinogen, acute phase proteins or immunoglobulin) or due to reducedpacking of red blood cells (anaemia). Other causes of a raised ESRinclude myeloma, polymyalgia rheumatica and autoimmune disease.

Question 48

A Temporal arteritisB Renal cell carcinomaC Colorectal cancerD Rheumatoid arthritisE Miliary tuberculosisF Acute pancreatitisG SchistosomiasisH SarcoidosisI Epstein–Barr infectionA 38-year-old man from Nigeria presents to his GP with progressive shortnessof breath, cough and painful rashes on his lower legs. Blood tests reveal amonocytosis. Chest X-ray demonstrates bihilar lymphadenopathy.

Answer 48

H SarcoidosisSarcoidosis (H) is a granulomatous disease characterized by the presenceof non-caseating granulomas in multiple organs, most commonly affectingthe lungs. Diagnosis of sarcoidosis is usually a matter of excludingother diseases but chest X-ray (bihilar lymphadenopathy), CT scanningand lung biopsy can all help. Blood tests commonly reveal a monocytosis;monocytes are contributory to the pathogenesis of granulomatousdisease. Other causes of monocytosis include brucellosis, typhoid, varicellazoster infection and chronic myelo-monocytic leukaemia (CMML).

Question 49

A Temporal arteritisB Renal cell carcinomaC Colorectal cancerD Rheumatoid arthritisE Miliary tuberculosisF Acute pancreatitisG SchistosomiasisH SarcoidosisI Epstein–Barr infectionA 66-year-old presents to his GP with severe weight loss over 1 month as wellas tiredness. Blood tests reveal an increased erythrocyte, haemoglobin anderythropoietin count.

Answer 49

B Renal cell carcinomaRenal cell carcinoma (RCC; B) is the most common type of renal cancer.Secondary polycythaemia may be associated with RCC as a resultof increased erythropoietin (EPO) production. Secondary polycythaemiacan be distinguished from primary polycythaemia as in the former thereis an increase in blood EPO levels, whereas in the latter EPO levelsdecrease. Other causes of secondary polycythaemia include chronichypoxia (high altitude, smoking, lung disease, cyanotic heart disease),renal disease (cysts, renal artery stenosis, hydronephrosis) and solidtumours (renal cell carcinoma and hepatocellular carcinoma).

Question 50

A Temporal arteritisB Renal cell carcinomaC Colorectal cancerD Rheumatoid arthritisE Miliary tuberculosisF Acute pancreatitisG SchistosomiasisH SarcoidosisI Epstein–Barr infectionA 24-year-old man has recently returned from a trip to Kenya. He presents tohis GP with abdominal pain, fever and on examination has hepatosplenomegaly.Blood tests reveal a marked eosinophilia.

Answer 50

G SchistosomiasisSchistosomiasis (G) is a parasitic disease caused by Schistosoma spp.It is particularly common in Asia, Africa and South America. The riskof bladder cancer is increased in urinary forms of schistosomiasis. Theimmune response to parasitic infection involves eosinophils and hencea marked eosinophilia is characteristic. Other causes of eosinophiliabesides parasitic infection include allergic disease (asthma, rheumatoidarthritis, polyarteritis), neoplasms (Hodgkin’s lymphoma, non-Hodgkin’slymphoma) as well as certain drugs (NSAIDs).