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.