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Recombinant factor VIII has biologic activity comparable to that of plasma factor VIII and is safe and efficacious for the treatment of hemophilia A.

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Summary Background The development of neutralizing antibodies, referred to as inhibitors, against factor VIII (FVIII) is a major complication associated with FVIII infusion therapy for the treatment of hemophilia A (HA). Previous studies have shown that a subset of HA patients and a low percentage of healthy individuals harbor non-neutralizing anti-FVIII antibodies that do not elicit the clinical manifestations associated with inhibitor development. Objective Assess HA patients' anti-FVIII antibody profiles as potential predictors of clinical outcomes. Methods A fluorescence immunoassay (FLI) was used to detect anti-FVIII antibodies in 491 samples from 371 HA patients. Results Assessments of antibody profiles showed that the presence of anti-FVIII IgG1, IgG2, or IgG4 correlated qualitatively and quantitatively with the presence of a FVIII inhibitor as reported by the Nijmegen-Bethesda assay (NBA). Forty-eight patients with a negative inhibitor history contributed serial samples to the study, including seven patients who had negative NBA titers initially and later converted to NBA-positive. The FLI detected anti-FVIII IgG1 in five of those seven patients prior to their conversion to NBA-positive. Five of 15 serial-sample patients who had a negative inhibitor history and a positive anti-FVIII IgG1 later developed an inhibitor, compared to 2 of 33 patients with a negative inhibitor history without anti-FVIII IgG1. Conclusions These data provide a rationale for future studies designed both to monitor the dynamics of anti-FVIII antibody profiles in HA patients as a potential predictor of future inhibitor development and to assess the value of the anti-FVIII FLI as a supplement to traditional inhibitor testing.

One hundred thirty-one patients followed at the New England Hemophilia Center (Worcester, MA) were tested for antibody to hepatitis C virus (HCV). All but two had used factor concentrate that had not undergone viral inactivation; two patients had used only cryoprecipitate. The overall prevalence of HCV antibody positivity was 76.3%. There was no significant difference in age or the amount of non-heat-treated factor concentrate used between the group that was HCV antibody positive and negative. There was also no significant difference between aminotransferase levels in the two groups. There was a positive association between HCV antibody and the presence of antibody to hepatitis B core antigen and antibody to human immunodeficiency virus. A group of 31 patients were tested twice for HCV antibody at intervals of 35 to 71 months. In this subset, 25 were repeatedly seropositive, 4 were repeatedly seronegative, and 2 went from seropositive to seronegative. These data confirm the previous impression that non-A, non-B hepatitis is a major sequela to the use of pooled coagulation factor concentrates. HCV infection may account for most of the chronic liver disease observed in this population. Anti-HCV testing of plasma donors and improved methods of viral inactivation should prevent new cases from developing.