Factor VIII Inhibitor — RACP Adult Medicine MCQ

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HardHaematologyFactor VIII InhibitorRACP Adult Medicine

A 55-year-old man with known severe haemophilia A on factor VIII prophylaxis develops a prolonged APTT that does not correct with a mixing study. His factor VIII level is very low despite increasing doses. Anti-factor VIII antibody titre (Bethesda assay) is 15 BU/mL. What has developed?

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Correct answer: C — Factor VIII inhibitor (alloantibody)

Factor VIII inhibitors (alloantibodies) develop in 20–30% of patients with severe haemophilia A, rendering factor VIII replacement ineffective. The diagnosis is confirmed by a Bethesda assay titre (inhibitor >5 BU is high-titre). A mixing study that does NOT correct indicates an inhibitor (whereas correction suggests factor deficiency). Management of acute bleeding requires bypassing agents (recombinant FVIIa or FEIBA/aPCC). Immune tolerance induction (ITI) with high-dose factor VIII is the strategy to eradicate the inhibitor. Emicizumab is now used as prophylaxis in inhibitor patients.

Reference: eTG – 2025 – Haematology; National Blood Authority – 2024 – Haemophilia Management