FRCPath Haem Part 1 MCQs-Morphology 507

A 7-year-old boy is referred with a history of recurrent jaundice, pallor and poor exercise tolerance since infancy. He has required multiple red cell transfusions and underwent splenectomy at the age of 5 years because of persistent splenomegaly and transfusion requirements.

Investigations reveal:

• Hb: 82 g/L

• MCV: 92 fL

• Reticulocyte count: 18%

• Unconjugated bilirubin: 58 µmol/L

• LDH: Increased

• Haptoglobin: Undetectable

Peripheral blood film demonstrates marked polychromasia, occasional nucleated red cells and echinocytes. There are also occasional irregularly contracted red cells.

Which of the following abnormalities is most likely responsible for the underlying red cell morphology?

A. Defective spectrin–ankyrin interactions resulting in membrane instability and loss of membrane surface area.

B. Impaired ATP generation resulting in failure of ATP-dependent membrane pumps and abnormal red cell hydration.

C. Defective globin-chain synthesis resulting in excess unmatched globin chains and oxidative membrane damage.

D. Defective hexose monophosphate shunt resulting in reduced NADPH production and increased susceptibility to oxidative stress.

E. Defective pyruvate oxidation resulting in accumulation of 2,3-bisphosphoglycerate and increased red cell membrane rigidity.