FRCPath Haem Part 1 MCQ- Gen Haem 449

A 26-year-old woman is referred to the haematology clinic because of lifelong intermittent jaundice and increasing fatigue. She reports no history of blood transfusions. Her father underwent splenectomy in his twenties for a chronic haemolytic disorder. Examination reveals mild scleral icterus and a spleen palpable 3 cm below the costal margin.

Investigations show:

• Hb: 109 g/L

• MCV: 91 fL

• MCHC: 372 g/L

• LDH: Mildly elevated

• Haptoglobin: Undetectable

• DAT: Negative

Blood film demonstrates numerous spherocytes but also occasional macrocytes.

The laboratory performs an eosin-5-maleimide (EMA) binding test. The patient : control fluorescence ratio is 0.82, which is reported as within the laboratory reference interval. Because of the apparent discrepancy, sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) is requested and demonstrates a quantitative deficiency of ankyrin.

Which of the following is the best explanation for the apparently normal EMA binding result?

A. EMA binding is normal in ankyrin deficiency because ankyrin is not an EMA-binding protein.

B. Reticulocytosis and macrocytosis may reduce the diagnostic sensitivity of EMA testing, producing an equivocal or falsely normal result.

C. EMA binding should only be interpreted when the DAT is positive.

D. SDS-PAGE is less specific than EMA testing, therefore the ankyrin deficiency is likely to be an incidental finding.

E. Hereditary spherocytosis caused by ankyrin deficiency is not associated with reduced Band 3 expression.