After thousands of hemophilic patients were infected with HIV and HCV, and thanks to major advances in biotechnology, recombinant factor VIII has emerged as a first-line or reference treatment for most factor VIII-deficient patients (hemophilia A). The development of neutralizing antibodies (inhibitors) is currently the most severe and feared complication in hemophilia A replacement therapy. The respective immunogenicity of plasma and recombinant factor VIII concentrates has been debated for many years, with multiple studies providing contradictory results.
More recent large-scale studies conducted with rigorous methodology have demonstrated lower immunogenicity of plasma factor VIII as compared to recombinant FVIII. In addition, so-called non-substitutive therapeutic approaches for hemophilia are available or under validation. However, most of these treatments cannot be used alone without additional factor VIII and do not allow inducing tolerance to exogenous factor VIII. Thus, factor VIII concentrates with low immunogenicity are and remain an essential option in the treatment of hemophilia.
This article sought to review the respective immunogenicity of plasma and recombinant factor VIII, while highlighting the essential current and future role of factor VIII in the treatment of hemophilia. Furthermore, we reviewed the characteristics and properties of a plasma factor VIII concentrate subjected to a unique double nanofiltration process during its purification (Factane®, LFB), making it a treatment option of choice in many indications.
Hemophilia, factor VIII, plasma-derived factor VIII, recombinant factor VIII, inhibitor