A patient with haemophilia A has a factor VIII inhibitor titre of 50 Bethesda units (BU). Which therapeutic strategy is indicated for acute bleeding in high-responder haemophilia A with inhibitors?

• A High-dose factor VIII concentrate — because high doses will overwhelm the inhibitor via mass action
• B Fresh frozen plasma — to replace all clotting factors including endogenous FVIII
• C Desmopressin (DDAVP) — releases endogenous vWF-FVIII complex from endothelial stores to replenish FVIII
• D Bypassing agents — recombinant activated factor VII (rFVIIa/NovoSeven) or activated prothrombin complex concentrate (APCC/FEIBA) — which bypass the need for FVIII by directly activating the extrinsic or prothrombinase pathway ✓

Explanation

High-responder inhibitors (>5 BU/mL) render conventional FVIII replacement ineffective because the antibody neutralises infused FVIII too rapidly. Bypassing agents are the standard for acute bleeding: rFVIIa (eptacog alfa) directly activates FX at the tissue factor-bearing cell surface independently of FVIII; FEIBA (anti-inhibitor coagulant complex) contains activated clotting factors (FIIa, VIIa, IXa, Xa) that bypass FVIII in the coagulation cascade. Emicizumab (a bispecific antibody mimicking FVIII bridge between FIXa and FX) is now also used prophylactically for inhibitor patients. High-dose FVIII is only used for low-titre inhibitors (≤5 BU). FFP contains insufficient FVIII concentration. DDAVP is effective only in mild haemophilia A (FVIII >5%) and vWD, not in haemophilia A with inhibitors.

Reference: Robbins & Cotran Pathologic Basis of Disease, 10th ed.

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Written and medically reviewed by the StethoPrep medical team.