[Immune coagulation disorders (excluding antiphospholipid syndrome]

During the course of replacement therapy, 22-30% of patients with severe hemophilia A develop alloantibody to factor VIII. Autoantibodies to coagulation factors rarely occur in elder individuals with previously normal hemostatic mechanisms or in patients with various underlying disorders. Although the great majority of the acquired inhibitors are directed to factor VIII, the antibodies may arise to every coagulation factor. The inhibitor antibodies directly inactivate specific clotting factor, or occasionally, they bind to a nonfunctional site, resulting in increased plasma clearance. In the last decade, we experienced 12 hemophilia A and 3 hemophilia B patients who developed factor VIII and factor VIII and factor IX inhibitor, respectively, 9 patients with autoantibody to factor VIII (acquired hemophilia), and 4 patients with acquired von Willebrand syndrome. Among 12 factor VIII inhibitors, 4 patients were identified to have inversion in the factor VIII gene, 1 with 4 bases deletion, and 1 with missense mutation resulting in G479R. Four of 9 patients with acquired hemophilia had underlying disorders of autoimmune hemolytic anemia, macroglobulinemia, urticaria, and pharyngeal cancer at the development of factor VIII inhibitor. Antibody to von willebrand factor was detected in 3 of 4 patients with acquired von Willebrand syndrome.