• hemophilia A hemophilia B;
  • inhibitors;
  • mortality

Summary. Background: Previous studies of the development of inhibitors and their impact on mortality have been small. Objectives: To examine the development of inhibitors in people with hemophilia in the UK and their effect on subsequent mortality. Patients: 6078 males with hemophilia A and 1172 males with hemophilia B registered in the UK Haemophilia Centre Doctors' Organisation database, 1977–98.Results: In severe hemophilia A inhibitors developed at rates of 34.4, 5.2 and 3.8 per 1000 years at ages <5, 5–14 and 15+years; cumulative risks at ages 5 and 75 were 16% and 36%. In hemophilia A the rate of inhibitor development decreased during 1977–90, but increased during the 1990s. In severe hemophilia B inhibitors developed at rates of 13.3 and 0.2 per 1000 years at ages <5 and 5+ and cumulative risks at ages 5 and 75 were 6% and 8%. With HIV, inhibitor development did not increase mortality. In severe hemophilia without HIV, inhibitor development doubled mortality during 1977–92, but during 1993–99 mortality was identical with and without inhibitors. In severe hemophilia without HIV but with inhibitors, mortality from causes involving bleeding decreased during 1977–99 (P = 0.001) as did mortality involving intracranial hemorrhage (P = 0.007). Conclusions: These data provide estimates of the rate of inhibitor development in hemophilia A and hemophilia B, and they show that the rate of inhibitor development has varied over time, although the reasons for this remain unclear. They also show that in severe hemophilia the substantial increase in mortality previously associated with inhibitors is no longer present.