Drug-induced anti-factor VIII antibodies: a systematic review.

Acquired hemophilia A is an uncommon but potentially life-threatening hemorrhagic disorder caused by the onset of autoantibodies against coagulation factor VIII. Acquired hemophilia A is most frequently associated with autoimmune diseases, solid tumors, lymphoproliferative diseases, pregnancy, and drug reactions. However, in approximately 50 percent of the patients no underlying disorder can be identified. Prompt diagnosis of this acquired bleeding disorder is essential for appropriate management aimed to control hemorrhage and suppress the inhibitor. Based on electronic and manual searches of the published literature, this review examines the current knowledge on drug-induced factor VIII autoantibodies. A total of 34 cases were identified, mostly related to a variety of agents, including antibiotics and psychiatric and immunomodulatory drugs. In particular there is increased evidence for an association between acquired hemophilia A and interferon given as treatment for hepatitis C virus infection. Although most inhibitors reported in the literature were at high titers (mean: 67.7 Bethesda Units/ml), their prognosis was good, as they disappeared in most cases after suspension of the involved drug or after immunosuppressive therapy (complete remission rate: 83.3%). However, further studies are needed to better elucidate the epidemiology, natural history, clinical relevance, and optimal treatment of drug-associated factor VIII autoantibodies.

Treatment of hepatitis C in hemophiliacs.

Hepatitis C virus (HCV) infection is a major cause of morbidity and mortality in hemophiliacs who received nonvirucidally treated large-pool clotting factor concentrates before 1986. In fact, although many hemophiliacs infected with HCV have a slow progression of liver disease, in a minority of them hepatitis evolves toward end-stage liver disease and hepatocarcinoma. Moreover, a significant percentage of HCV-infected hemophiliacs were also coinfected with human immunodeficiency virus (HIV), which can accelerate the progression of liver disease. Thus, the aim of anti-HCV therapy is to interrupt the chronic infection in order to prevent the progression of hepatitis to cirrhosis, liver decompensation, cancer and, ultimately, death. In this review we present the literature data on anti-HCV treatment in hemophiliacs. Combination therapy with interferon (IFN) and ribavirin has improved the poor results obtained with IFN monotherapy and has become the standard treatment of chronic hepatitis C. Given the positive results obtained with pegylated interferon plus ribavirin in nonhemophiliacs, ongoing trials are evaluating this promising therapy in HCV-chronically infected hemophilic patients; preliminary results show a sustained response rate similar to that in patients without coagulopathy. Finally, based on the encouraging results in coinfected nonhemophiliacs, anti-HCV treatment should also be considered for those HIV-positive hemophiliacs in whom anti-retroviral treatment has stabilized the HIV infection.