Inhibitor incidence in hemophilia A patients intensively treated with continuous infusion of factor VIII

Continuous infusion (CI) of factor VIII is an advantageous method for intensive factor replacement in hemophilia. However, recent reports on inhibitor development in several patients treated with CI, particularly in patients with moderate/mild haemophilia pointed to an additional possible safety issue of this treatment method, which needs to be studied carefully. Our survey on current practice of CI in 22 European Comprehensive Haemophilia Centres demonstrated that 13 (59%) centres use CI in the settings of surgery and major bleeds. These centres commonly use adjusted dose CI method, employing portable mini-pumps or syringe pumps for prolonged infusion of small volumes of concentrated FVIII. Inhibitor incidence was evaluated in a cohort of 742 patients who received a total of 1079 CI treatments. The overall incidence of inhibitor after intensive treatment with CI of FVIII was low, only nine (1.2%) patients developed inhibitor, 3/659 (0.45%) severe and 6/83 (7.2%) mild. Further analysis of inhibitor patients revealed the presence of several potential confounding risk factors in this group: