You are on page 1of 12

Hematology

A 7 year old boy presents with pallor. He was a term 2.89kg infant born to a healthy Oriental mother. He is fully immunised, and on no medications. Hb 10.2 g/dl, MCV 69. He is treated with oral iron for three months, but there is no change in the FBC. A film shows Heinz bodies, target cells, anisopoikilocytosis and reticulocytes. Supravital staining shows inclusions of precipitated haemaglobin. What is the most likely diagnosis? Available marks are shown in brackets 1) 2) 3) 4) 5) Marrow failure Iron deficiency Occult blood loss Haemaglobinopathies eg Sickle, Thalassaemia Malignancy [0] [0] [0] [100] [0]

Comments: The history of mild pallor associated with microcytosis unresponsive to iron suggests a minor haemaglobinopathy. The film appearances and Hb electophoresis confirm alpha thalassaemia trait in this case. Which one of the following is true of IgE? Available marks are shown in brackets 1) 2) 3) 4) 5) Is present in plasma in the same concentration as IgG Is increased acutely in an asthmatic attack Crosses the normal placenta Is increased in the serum of atopic individuals Is involved in type 2 hypersensitivity [0] [0] [0] [100] [0]

Comments: IgG is the predominant form of immunoglobulin in plasma at a concentration around 10,000 times that of IgE. IgG crosses the placenta to confer immunity to the fetus but IgE does not. IgE is involved in arming mast cells and basophils. IgE causes mast cells to release vasoactive amines, such as histamine, producing an inflammatory response which can result in a type I hypersensitivity reaction. IgE is responsible for allergen-mediated diseases such as anaphylaxis, asthma and atopy. Total serum IgE is frequently increased in those with atopy but serum IgE does not rise acutely during an asthmatic attack.

A 16 year old girl presents with bilateral cervical lymphadenopathy. Her lymph node biopsy reveals a

Hematology

nodular sclerosing Hodgkins disease. Which one of the following features indicates a poorer prognosis? Available marks are shown in brackets 1) 2) 3) 4) 5) Fatigue Mediastinal mass of 3cm Night sweats Pruritis Recent Epstein-Barr virus infection [0] [0] [100] [0] [0]

Comments: Important prognostic features in HD are Stage - B symptoms- Fever/ night sweats and weight loss - Mass > 10 cm Therefore although fatigue and pruritus common, have no prognostic significance. EBV infection commonly associated with HD but has no prognostic significance. A 17 year old male with glucose-6-phosphate dehydrogenase deficiency presents with tiredness and is noticed to be jaundiced. These features have developed since he developed a mild chest infection one week ago. Which one of the following is the most likely haematological finding? Available marks are shown in brackets 1) 2) 3) 4) 5) Haemoglobinuria low mean cell volume Positive direct antiglobulin test Reduced reticulocyte count Spherocytes present on blood film [100] [0] [0] [0] [0]

Comments: G6PD deficiency is a red cell enzymopathy that can lead to acute intravascular haemolysis after exposure to certain drugs, infection etc. You would therefore get haemoglobinuria but would not get a positive direct antiglobulin test. The MCV and reticulocyte count would be high due to haemolysis. There is a form of G6PD deficiency where there is a chronic low level haemolysis, where there are spherocytes seen- but the clinical information points to intravascular haemolysis after an infection.

A 6 month old boy is noted to be slightly pale. Otherwise he has been perfectly healthy and well. He was born at 35+5/40 weighing 2.4kg and there were no neonatal problems.

Hematology

On examination he has a tinge of jaundice in the scelerae. His temperature is 36.6C (tympanic) with RR of 25/min and HR of 100/min. He has 3 cm of spleen. What is the most likely diagnosis? Available marks are shown in brackets 1) 2) 3) 4) 5) Haemaglobinopathies eg Sickle, Thalassaemia Iron deficiency Occult blood loss Haemolytic anaemia, congenital or acquired Malignancy [0] [0] [0] [100] [0]

Comments: The history suggests mild anaemia, probably due to haemolysis in view of the icterus and splenomegaly. The likely diagnosis is therefore hereditary spherocytosis. Blood film (and HP) contain microspherocytes (due to a loss of membrane, and therefore surface area so that the area of central pallor is lost). It is a common, usually autosomal dominant, genetic disorder, affecting 1:2000-1:5000 caucasians. Clinical features are very variable (may be diagnosed at birth (severe), in adulthood or not at all. An 18 year old Asian female is noted to have gingival hypertrophy by her dentist. Which of the following is most likely to be responsible for her presentation? Available marks are shown in brackets 1) 2) 3) 4) 5) carbamazepine scurvy lead poisoning phenytoin sodium valproate [0] [0] [0] [100] [0]

Comments: The inclusion of 'asian' descent in this question is intended as a distractor. Gum hypertrophy may be seen in conditions such as acute myeloid leukaemias and with drugs such as phenytoin. Scurvy (vitamin C deficiency) is associated with bleeding gums. Lead toxicity is associated with pigmentation of the gingiva. Carbamazepine is not associated with gingival hyperplasia but recognised SEs include ataxia, drowsiness and blood dyscrasias.

A 3 year old girl presents with pallor, lethargy and bruising. She has been unwell for about 3 weeks, but seems to have deteriorated over the past few days. She was born at 40+2/40 gestation weighing 3.0kg and there were no neonatal problems. On examination she appears very pale, and has petechiae over the palate and arms. She looks unwell.

Hematology

She is on the 25th centile for height and weight and has no dysmorphic features. What is the most likely diagnosis? Available marks are shown in brackets 1) 2) 3) 4) 5) Marrow failure Iron deficiency Occult blood loss Haemaglobinopathies eg Sickle, Thalassaemia Malignancy [100] [0] [0] [0] [0]

Comments: The history suggests bone marrow failure of subacute onset, with at least 2 cell lines involved (red cells and platelets). The presence of hepatosplenomegaly or lymphadenopathy might suggest acute leukaemia, but in their absence aplastic anaemia is a strong possibility. This can be confirmed by bone marrow aspirate, which shows marrow hypoplasia. Most are idiopathic. Underlying congenital causes are present 20%, and include Fanconi anaemia, Blackfan Diamond, Swachmann, Cartilage Hair Hypoplasia and Pearson syndrome. Underlying acquired causes include infections (EBV, parvovirus, HIV), toxins and drugs, pregnancy and transplant-related. A 16 month old West Indian by is referred because of reduced exercise tolerance. He has never been cyanosed, but seems to lack stamina compared with his peers. He was born at 39/40 weighing 4.1kg and there were no neonatal problems. On examination he appears pale but well nourished. He has slightly yellow sclerae. He is on the 75% for height and weight. He has a grade 2/6 ejection systolic murmur at the left sternal edge and 3 cm of spleen palpable. What is the most likely diagnosis? Available marks are shown in brackets 1) 2) 3) 4) 5) Marrow failure Iron deficiency Occult blood loss Haemaglobinopathies eg Sickle, Thalassaemia Malignancy [0] [0] [0] [100] [0]

Comments: The history suggests mild haemolytic anaemia. His ethnicity suggests Sickle cell disease, which can be confirmed by haemaglobin electrophoresis. Complications include sequestration crisis, infections (encapsulated bacteria such as pneumococcus, staph and salmonella), painful crisis, stroke, cholecystitis, avascular necrosis of the femoral head and priapism. A 3 year old boy presents with a 2 week history of pallor and lethargy. Today mother has noticed that he has a low grade fever and some spots on his chest. He was born at 36/40 gestation weighing 2.6kg. He was diagnosed with Down's syndrome in the neonatal period. He has had glue ear requiring grommet insertion. On examination he has a temperature of 37.8C (tympanic), RR of 15/min and HR of 100/min. He looks pale and lethargic. He has petechiae and ecchymoses over his chest. He has 3 cm of liver edge

Hematology

palpable. What is the most likely diagnosis? Available marks are shown in brackets 1) 2) 3) 4) 5) Marrow failure Iron deficiency Occult blood loss Haemaglobinopathies eg Sickle, Thalassaemia Malignancy [0] [0] [0] [0] [100]

Comments: The history suggests a rapid progression of bone marrow failure, with features of abnormalities in all three cell lines: red cells, white cells and platelets. The most likely cause is acute leukaemia. The incidence is 20-30x increased in children with Down's syndrome. The diagnosis is confirmed by bone marrow biopsy. Treatment will be guided by the precise cell types involved. Which of the following statements concerning abnormalities of the haemoglobin molecule is true? Available marks are shown in brackets 1) 2) 3) 4) 5) Alpha thalassaemia is due to a deficiency of beta-chain production HbS is caused by a single base mutation on the beta-chain genes for the alpha and beta chains are located on the same chromosome in thalassaemia persistance of HbF is an adverse prognostic sign oliguneoclitide probes may assist in the diagnosis of haemoglobinopathies [0] [100] [0] [0] [0]

Comments: Alpha Thalassaemia is due to abnormalities of the alpha chain. Persistence of HbF has survival advnatages in severely affected subjects. C-alpha 16, beta 11. e-Hb electrophoresis(Dr Shu Ho)

A 2 day old boy presents with rapidly increasing unconjugated jaundice. He was born at 39+2/40 weighing 2.91kg and there were no neonatal problems. Pregnancy was uncomplicated. FBC 12.0 g/dl, reticulocytes 22%. Film shows polychromasia and nucleated red cells. DCT -ve. Mother and baby both O+ve. What is the most likely diagnosis? Available marks are shown in brackets

Hematology

1) 2) 3) 4) 5)

Marrow failure Haemolytic anaemia, congenital or acquired Occult blood loss Haemaglobinopathies eg Sickle, Thalassaemia Malignancy

[0] [100] [0] [0] [0]

Comments: The picture of severe unconjugated hyperbilirubinaemia without evidence of isoimmunisation suggests a red cell membrane or enzyme defect. G6PD deficiency, Pyruvate Kinase deficiency, hereditary spherocytosis and hereditary elliptocytosis are the archetypes for these 2 groups. Hereditary spherocytosis is due to spectin deficiency resulting in abnormal cytoskeleton and reduced cell deformation. The percentage of spherocytes at particular concentrations of Hb allow the diagnosis to be made by Coulter counter, rather than waiting to do osmotic fragility when they are older. An 18 month old girl presents with pallor. She has always been a poor eater, and survives mainly on bottles of milk. She was born at 37+2/40 weighing 2.7kg and there were no neonatal problems. On examination she looks pale but not icteric. Her temperature is 36.8C(tympanic), HR 100/min and RR 15/min. She has a grade 2/6 ejection murmur at the left sternal edge. She has no hepatosplenomegaly nor bruising. What is the most likely diagnosis? Available marks are shown in brackets 1) 2) 3) 4) 5) Marrow failure Iron deficiency Occult blood loss Haemaglobinopathies eg Sickle, Thalassaemia Malignancy [0] [100] [0] [0] [0]

Comments: The history suggests an inadequate diet following difficulties in weaning. She almost certainly has iron deficiency anaemia. A full blood count shows Hb 3.3g/dl, with MCV of 64. Treatment with 3/12 of oral iron will replenish iron stores. Mother should be given dietetic advice.

A 17 year old girl underwent emergency splenectomy after a domestic accident. Which one of the following organisms is most likely to cause life-threatening infection in the future? Available marks are shown in brackets 1) 2) 3) 4) 5) Actinomycosis Haemophilus influenzae Pseudomonas aeruginosa Staphylococcus aureus Streptococcus pneumoniae [0] [0] [0] [0] [100]

Hematology

Comments: Following splenectomy a person is at risk of Streptococcus pneumoniae , Haemophilus influenzae, Nesseria meningitidis, Escherichia coli and Pseudomonas aeruginosa. By far the most common is Streptococcus pneumoniae- which can cause life threatening infection. A 4 year old girl presents with extensive bruising over the trunk, legs and palate. She had an URTI 4 weeks ago, but has otherwise been well. 39+5/40 3.8kg delivery, with no neonatal problems. No FH of note. On examination she is well. Temperature is 36.7C (tympanic), HR 90/min, RR 20/min. Extensive fresh bruising of irregular shape over trunk, thighs and shins. Old bruises over shin. What is the most likely diagnosis? Available marks are shown in brackets 1) 2) 3) 4) 5) Streptococcal infection Thrombocytopaenia Trauma/ child abuse Vasculitis eg HSP Viral infection [0] [100] [0] [0] [0]

Comments: This girl had a presumed viral illness a month ago and now presents with sudden onset of extensive bruising. The likely diagnosis is Idiopathic thrombocytopaenic purpura. This can be confirmed by an FBC and film, which shows isolated thrombocytopaenia. Most can be managed conservatively, with the platelet count recovering spontaneously over 1-4 weeks. IVIG or steroids may accelerate recovery. If steroid therapy is contemplated it should be preceded by a bone marrow biopsy to exclude an thrombocytopaenic presentation of leukaemia.

A 7 year old girl presents with a 3 day history of rash and ankle swelling. She had a cold 4 weeks previously, but has otherwise been healthy. 39+1/40, 2.96kg. No neonatal problems. No drugs or medications. Fully immunised. On examination, she has palpable non-blanching purple spots 1-4 mm in diameter especially over the shins and buttocks. Her left ankle is swollen, warm and tender, with restricted movement. What is the most likely diagnosis? Available marks are shown in brackets 1) 2) 3) Streptococcal infection Thrombocytopaenia Trauma/ child abuse [0] [0] [0]

Hematology

4) 5)

Vasculitis eg HSP Viral infection

[100] [0]

Comments: The history is of preceding URTI followed by vasculitis on the shins and buttocks, and ankle swelling. This is classical of Henoch-Schonlein purpura. The pathological lesion is a vasculitis, hence the lesions are often palpable. In contrast thrombocytopaenic purpura are not raised. The classical features are rash, joint swelling, haematuria, and GI symptoms (vomiting, abdominal pain, PR bleeding, occasional intussusception).

Which of the following haematological disorders is inherited as an autosomal recessive condition? Available marks are shown in brackets 1) 2) 3) 4) 5) Antithrombin III deficiency Protein C deficiency Glucose-6-phosphate dehydrogenase deficiency Pyruvate kinase deficiency Acute intermittent porphyria [0] [0] [0] [100] [0]

Comments: Anti-thrombin 3 (AT3) is a plasma inhibitor protein that blocks the enzymatic activity of some serrin proteases coagulation factors. The activity of this inhibitor in increased by heparin. AT3 is synthesised by the liver, is not Vitamin K dependent, and can be consumed during DIC. Normal newborns have a

Hematology

reduced activity. Congenital AT3 deficiency is an autosomal dominant. Treatment of thrombotic in these events in these patients may be difficult. Protein C is an inhibitor that once activated inhibits clot formation and enhances fibrinolysis. It is liver synthesised and Vitamin K dependent. Protein C is converted to an active enzyme by a thrombinthrombomodulin complex on the endothelial cell surface. Activated protein C inhibits a plasminogen activator inhibitor, which results in enhanced fibrinlysis, and, with protein S as a co-factor, inhibits the clotting of the activated factors 5 and 8 by limited proteolosis. Activated protein C thus controls the conversion of factor 10 to 10a and prothrombin to thrombin. Congenital deficiency is an autosomal dominant trait. Acquired deficiency may occur in association with infection. Glucose-6-phosphate dehydrogenase deficiency is the most important disease of the pentose phosphate pathway, and is responsible 2 clinical syndromes: an episodic haemolytic anaemia induced by infections or certain drugs, and a spontaneous chronic non-spherocytic haemolytic anaemia. The deficiency is Xlinked, and heterozygous females are resistant to falciparum infections. There are a large number of abnormal alleles causing disease of vastly different severity. Pyruvate kinase deficiency is a rare congenital haemolytic anaemia inherited as an autosomal recessive. Generation of ATP within the red cell is impaired resulting in an abnormally high concentration of 2,3,DPG in the red cell, which inhibits the enzymes of the pentose phosphate pathway. Clinical manifestations vary from severe neonatal haemolysis, to a mild well compensated haemolysis first noted in adulthood. Acute intermittent porphyria is an autosomal dominant disorder resulting from partial porphobilinogen deaminase deficiency in the cytosol of all tissues including erythrocytes. Clinical expression of the disease is linked to environmental or acquired factors such as nutritional status, drugs, steroid or chemicals. The major abnormality is of the peripheral, autonomic or CNS. Major symptoms are abdominal pain, nausea, vomiting, constipation or diarrhoea. In severe cases the urine develops a port wine colour due to the high content of porphobilin, an auto-oxidation product of PBG. Hypertension and neuropathy are common, with muscle weakness, cranial nerve abnormality and seizures. Copyright 2002 Dr Colin Melville

A patient with end stage renal disease is receiving haemodialysis and erythropoietin. Which of the following does Erythropoietin therapy cause? Available marks are shown in brackets 1) 2) 3) 4) 5) Benign intracranial hypertension Myositis Hypotension Seizures Osteoporosis [0] [0] [0] [100] [0]

Comments: Hypertension is a frequent problem associated with erythropoietin and may induce seizures. A particular symptom is the onsent of sudden stabbing migraine-like headache and should raise awareness to the possibility of hypertensive crisis. Other adverse effects of treatment with erythropoietin include hyperkalaemia in uraemic patients, increased PCV (especially with misuse by normal individuals), thrombocythaemia, shunt thrombosis, induction of iron deficiency, skin rashes, urticaria and flu-like

Hematology

illness. A 17 year old male with glucose-6-phosphate dehydrogenase deficiency presents with tiredness and is noticed to be jaundiced. These features have developed since he developed a mild chest infection one week ago. Which one of the following is the most likely haematological finding? Available marks are shown in brackets 1) 2) 3) 4) 5) Haemoglobinuria low mean cell volume Positive direct antiglobulin test Reduced reticulocyte count Spherocytes present on blood film [100] [0] [0] [0] [0]

Comments: G6PD deficiency is a red cell enzymopathy that can lead to acute intravascular haemolysis after exposure to certain drugs, infection etc. You would therefore get haemoglobinuria but would not get a positive direct antiglobulin test. The MCV and reticulocyte count would be high due to haemolysis. There is a form of G6PD deficiency where there is a chronic low level haemolysis, where there are spherocytes seen- but the clinical information points to intravascular haemolysis after an infection.

A 17 year old girl who had completed treatment for acute lymphoblastic leukaemia six months previously, presents with a short history of right hip pain. What is the most likely diagnosis? Available marks are shown in brackets 1) 2) 3) 4) 5) Avascular necrosis of the femoral head Gout Osteoarthritis Pseudogout Septic arthritis [100] [0] [0] [0] [0]

Comments: Avascular necrosis of the femoral headcan occur as a consequence of her treatment. At age 17, osteoarthritis is particularly unlikely. Gout too is unlikely (considering she completed treatment six months ago) unless she had relapsed (high white cell count) or had some other risk factors. She would be considered to be no more likely to get septic arthritis or pseudogout than anyone who had not previously had acute lymphoblastic leuaemia, if in remission.

Hematology 10

In sickle cell disease: Available marks are shown in brackets 1) 2) 3) 4) 5) The Sickledex test involves adding a reagent to blood, which allows the nature of the haemoglobinopathy to be determined It is caused by the substitution of glutamic acid by valine at position 4 on the beta chain of haemoglobin The erythrocytes of Haemoglobin AS patients can sickle at a PO2 of 5 to 6 kPa (40 - 50 mmHg) The erythrocytes of Haemoglobin SC patients may sickle at a PO2 of 4 kPa (30 mmHg) Exchange transfusions prior to major surgery on HbSS patients, aims to lower the HbS concentration to 60% [0] [0] [0] [100] [0]

Comments: Sickle cell disease is a haemoglobinopathy caused by the substitution of glutamic acid by valine at position 6 (from the N-terminal) of the beta chain. Inherited as an autosomal gene, heterozygous (HbAS) and homozygous (HbSS) forms exist. A low partial pressure of oxygen (PO2) causes HbS to polymerise and precipitate, resulting in sickling of the erythrocyte. HbSS patients sickle at PO2 of 5 - 6 kPa and HbAS patients sickle at PO2 of 2.5 - 4 kPa. A mild disease is produced when heterozygotes for HbS combine with other haemoglobins e.g. Haemoglobin C, thus creating HbSC. Sickling occurs at around 4 kPa. Diagnosis of sickle cell disease requires the detection of HbS. The Sickledex test involves the addition of reagent to blood; turbidity confirming the presence of HbS, but it gives no information on other haemoglobins. Haemoglobin electrophoresis is the only investigation that determines the nature of the haemoglobinopathy.

A 16-year-old girl with sickle cell disease presented with malaise and rapidly increasing dyspnoea. A full blood count showed: Hb 5.1 g/dL Reticulocyte count 5.5 x 109/L (25-85) What is the most cause? Available marks are shown in brackets 1) 2) 3) 4) 5) Epstein-Bar virus Hepatitis E virus Human immunodeficiency virus Human papillomavirus-16 (HPV 16) Parvovirus B19 [0] [0] [0] [0] [100]

Comments: Aplastic crisis in SSA is caused by infection with the Parvovirus B19. The virus infects red cell progenitors in bone marrow, resulting in cessation of erythropoiesis and a very rapid drop in haemoglobin. The condition is self-limited, with bone marrow recovery occurring in 7-10 days, followed by brisk reticulocytosis.

Hematology 11

A man with haemophillia has come to you for genetic counselling. Which of the following statements would be incorrect regarding the inheritance of his condition. Available marks are shown in brackets 1 ) His mother is certainly the carrier from whom he inherited the disease. 2 ) All his daughters will be carriers. 3 ) All his sons will be normal. 4 ) The condition is transmitted in an X linked recessive fashion. 5 ) If his sister has an affected boy she must be a carrier. Comments: Both his parents may have been unaffected or non-carriers and the disease could occur from of a spontaneous mutation. His daughters will inherit the abnormal gene from their father and be carriers and his sons will be unaffected. The disease is transmitted in an X-linked recessive fashion. If his sister has an affected son and a brother with the condition, the disease is inherited and she must be a carrier. [100] [0] [0] [0] [0]

Which of the following is inherited as sex linked recessive Available marks are shown in brackets 1) 2) 3) 4) 5) Idiopathic thrombocytopenia Glucose 6 phosphate dehydrogenase deficiency Neurofibromatosis Von Willebrands disease Hereditary spherocytosis [0] [100] [0] [0] [0]

Comments: Idiopathic thrombocytopenia is not a genetic disorder. G6PDH is X-linked recessive. Neurofibromatosis is autosomal dominant. Von Willebrands disease is mostly inherited in a dominant fashion, but recent case reports suggest some forms of the disease are autosomal recessive. HS is autosomal dominant.

Hematology 12