Serological markers of autoimmunity in patients with hemophilia A: the role of hepatitis C virus infection, alpha-interferon and factor VIII treatment in skewing the immune system toward autoreactivity

The aim of this study was to investigate whether the immune system of patie nts with hemophilia A is skewed toward an aspecific activation and to ident ify the causative factors. It is well known that an immune derangement does exist in patients with hemophilia A. At least three factors potentially pl ay a role: hepatitis C virus (HCV) infection, alpha-interferon therapy and the administration of factor VIII (FVIII). Sixty human immunodeficiency vir us (HIV)-negative patients with severe or moderate hemophilia A were studie d retrospectively. The serological markers of autoimmunity were evaluated a nd the results correlated with anti-HCV antibodies, FVIII treatment and alp ha-interferon therapy. The role of these factors in the development of the anti-FVIII antibody was estimated concomitantly. The prevalence of autoanti bodies and anti-FVIII antibodies was higher in HCV-positive than in HCV-neg ative patients before any treatment, although the difference was not statis tically significant. The administration of FVIII further influenced the dev elopment of autoantibodies both in HCV-negative and HCV-positive patients, with no difference being observed between the two groups. As expected, fewe r HCV-negative than HCV-positive patients developed anti-FVIII antibodies a fter administration of FVIII (31.8% versus 38%, respectively). Therapy with alpha-interferon did not seem to enhance significantly the risk of develop ing autoantibodies nor anti-FVIII antibodies. We observed a high prevalence of humoral signs of autoimmunity among patients with hemophilia A. Treatme nt with FVIII concentrate is probably the most important triggering factor. Monitoring these patients for autoimmune manifestations is recommended. Bl ood Coag Fibrinol 10:393-397 (C) 1999 Lippincott Williams & Wilkins.