Acquired hemophilia: diagnosis and management

In this review, we describe our current understanding of the mechanisms of autoimmunity, the effect of antibodies on factor VIII, and immunosuppressant agents currently in use. Factor VIII autoantibodies may arise because of dysregulation of the immune system leading to increased autoreactivity or to clonal expansion of reactive B cells. Patients generally have several antibodies directed against a variety of functional epitopes. These antibodies may inhibit binding of factor VIII to the von Willebrand factor or phospholipid, prevent the association of factor VIII with factor IXa, block the binding of factor Xa to factor VIII, or interfere with the formation of the factor VIIIa-factor IXa-phospholipid (tenase) complex. Additionally, antibodies have been described that catalyze the hydrolysis of factor VIII. The production of antibodies has been effectively suppressed by a number of drugs, including steroids, cyclophophamide, cyclosporine, and rituximab. Beginning with a short course of steroids and then adding one or more agents as needed is a currently accepted strategy for restoring normal factor VIII levels.