Acquired Hemophilia A: A Frequently Overlooked Autoimmune Hemorrhagic Disorder

Figure 1

Structure of the coagulation factor VIII (FVIII) molecule. The numbers indicate amino acid positions. Plasma FVIII is a heterodimer composed of a heavy chain (domains A1, A2, and B) and a light chain (domains A3, C1, and C2). Noncovalent binding of FVIII with von Willebrand factor (VWF) protects circulating FVIII from being inactivated by activated protein C. The binding sites of VWF, phospholipids (PL), and other coagulation factors (activated factor IX [FIXa], factor X [FX], and activated FX [FXa]) are also indicated. FVIII is cleaved and activated by thrombin and FXa at residues 372 and 740 within the heavy chain and at residue 1689 within the light chain. Inhibitors impair FVIII activation by interfering with thrombin-catalyzed cleavage or FVIII interactions with VWF, FIXa, FX, and PL. AR: acidic region.