Approximately 30% of patients with severe hemophilia A will develop inhibitory antibodies to factor VIII (fVIII inhibitors). In addition, autoimmune antibodies to fVIII can develop in non-hemophiliacs, producing acquired hemophilia A, which frequently produces life- or limb-threatening bleeding. Patients with congenital hemophilia who develop inhibitors usually have a polyclonal antibody response directed against the A2 and C2 domains of fVIII. Patients with acquired hemophilia typically have a more limited B-cell epitope response with antibodies directed against the A2 or C2 domain not both. Classical anti-C2 antibodies inhibit the binding of fVIII to phospholipid membranes and to von Willebrand factor. We recently have identified anti-C2 antibodies that inhibit the activation of fVIII, but do not inhibit the binding of fVIII to phospholipid membranes or to von Willebrand factor. These non-classical inhibitors are found in the plasmas of most inhibitor patients (
Disclosures: No relevant conflicts of interest to declare.