Inhibitors in haemophilia: pathophysiology

Development of inhibitors to coagulation factors is one of the major problems faced by people with haemophilia. Up to a third of patients, following treatment with factor concentrates, will develop an antibody (inhibitor) to that factor, rendering it inactive, and leaving the patient at risk from life-threatening bleeding. Evidence shows that this immune response is T-cell-dependent, but as yet, the epitopes responsible have not been identified. Risk for inhibitor development is highest within the first 50 days of treatment, with reactions being rare after 200 days. The risk is mediated by the major histocompatibility complex class of the patient, and by mutations in the factor VIII genotype, with large deletions conferring greatest risk.