Inhibitors in congenital coagulation disorders

The development of inhibitory 'allo' antibodies to a deficient coagulation factor is arguably now the most severe and important complication of clotting factor concentrate exposure in haemophilia and other congenital coagulation disorders. Furthermore, development of an inhibitor to the factor VIII or factor IX transgene product remains a significant concern in gene therapy protocols for haemophilia. Although the development of an inhibitor does not usually change the rate, initial severity or pattern of bleeding, it does compromise the ability to manage haemorrhage in affected individuals, resulting in a greater rate of complications, cost and disability. The purpose of this review is to summarize current understanding of the epidemiology, immunobiology, laboratory evaluation and management of inhibitors arising in patients with congenital coagulation disorders. An attempt has been made to focus on recent advances in the immunology of inhibitors, and to speculate on their potential clinical application.