FRCPath Haem Part 1 EMQs-General Haem 55 and 56

Options (each used once, more than once, or not at all):

A. Pyruvate kinase deficiency

B. Glucose-6-phosphate dehydrogenase deficiency

C. Increased 2,3-bisphosphoglycerate

D. Decreased oxygen affinity of haemoglobin

E. Reticulocytosis masking enzyme deficiency

F. Heinz body formation

G. Echinocyte (burr cell) formation

H. Oxidative stress–induced hemolysis

I. ATP depletion in red cells

J. X-linked inheritance

Questions

Q1

A 24-year-old man of African ancestry presents with dark urine and jaundice 48 hours after starting trimethoprim-sulfamethoxazole. He reports similar episodes during childhood illnesses. Examination reveals mild scleral icterus but no splenomegaly. Hb is 95 g/L, reticulocytes are elevated, and LDH is raised. Blood film shows bite cells and blister cells.

Q2

A 17-year-old patient with a lifelong history of anemia presents with worsening fatigue. He has splenomegaly and gallstones. Hb is 85 g/L, reticulocytes are elevated. Blood film shows anisopoikilocytosis with numerous echinocytes. Enzyme assay reveals reduced pyruvate kinase activity.

Q3

A 28-year-old woman with chronic hemolytic anemia due to a glycolytic enzyme defect has relatively mild symptoms despite low haemoglobin levels. Laboratory testing shows elevated 2,3-BPG levels.

What is the main physiological adaptation explaining her relatively preserved exercise tolerance?

Q4

A 6-year-old child is investigated for chronic hemolysis. Initial enzyme assays for pyruvate kinase are within normal range. However, the reticulocyte count is markedly elevated. A repeat test after stabilization confirms enzyme deficiency.

Q5

A 35-year-old man with chronic hemolysis due to a glycolytic defect has a right-shifted oxygen dissociation curve on analysis.

What is the biochemical basis of this shift?

Q6

A 21-year-old male presents with acute hemolysis after eating fava beans. Family history reveals multiple affected male relatives on the maternal side. His sister is asymptomatic.

Q7

A patient with chronic non-spherocytic hemolytic anemia is found to have a deficiency in a key glycolytic enzyme. Red cells show reduced survival due to membrane rigidity and inability to maintain ion gradients.

What is the primary metabolic defect leading to hemolysis?

Q8

A peripheral blood smear from a patient with acute hemolysis shows inclusion bodies that stain with supravital dyes. These inclusions represent denatured haemoglobin due to oxidative damage.

Q9

A 30-year-old patient reports multiple episodes of jaundice triggered by infections and certain medications. Between episodes, haemoglobin levels are normal. No splenomegaly is noted.

Q10

A patient with pyruvate kinase deficiency is noted to have increased levels of 2,3-BPG. Despite anemia, oxygen delivery to tissues is relatively preserved.

What is the direct effect of increased 2,3-BPG on haemoglobin?