Testing for Anti-factor VIII Allo- and Autoantibodies using Functional Bethesda and Anti-FVIII IgG Immunoassay

Introduction: The primary aim in the treatment of patients with hemophilia A is the prevention of bleeds with factor VIII (FVIII) replacement therapy. One major adverse event of factor VIII replacement therapy is the developement of alloantibodies (FVIII inhibitors). These antibodies may show a neutralizing effect on FVIII activity, resulting in an inadequate recovery after intravenous FVIII application and an increase in bleeding episodes. In hemophilia care the repetitive examination of the patients’ inhibitor status is mandatory. The functional Bethesda assay has a broad acceptance as a standard procedure, although it is difficult in performance, standardization and costly. Immunoassays for detection of Factor VIII antibodies have been introduced. Data from a nationwide cohort study in the US suggests to replace the costly clotting assay by an immunoassay using recombinant Factor VIII as antigen.

Methods: FVIII inhibitor testing was performed with dilutional FVIII clotting assay (Technoclone, Factor VIII Inhibitor Kit™) and anti-FVIII immunoassay (Hyphen Biomed, Zymutest™ anti-FVIII IgG mono strip).

Results: We examined 322 blood samples obtained from 203 pediatric and adult with haemophilia A on FVIII replacement therapy.

Conclusion: Discordant results were only detected in the Bethesda assay negative results (< 0,4 BU). We found a considerable number of borderline reactive samples (28%, 91/322) and 8% (26/322).

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