Factor VIII Inhibitor Assays: Methodology, Shortcomings, and Challenges

Review ARTICLE

Factor VIII Inhibitor Assays: Methodology, Shortcomings, and Challenges

M van Geffen, M Dardikh  and B Verbruggen
Affiliation: Laboratory of Hematology, Department of Laboratory Medicine, Radboud University Nijmegen Medical Center, Nijmegen, The Netherlands


ABSTRACT

Development of inhibitory antibodies against factor VIII is a serious complication in the treatment of hemophilia patients, as these antibodies inactivate factor VIII, resulting in an increased bleeding tendency and morbidity. The clinical manifestation of inhibitors has to be analyzed by objective laboratory tests to specify the exact nature of the inhibitor. Here, the inhibitor assays, especially the Bethesda assay and the Nijmegen assay, are discussed including their methodological shortcomings. This paper also discusses the epitope specificity of the inhibitor assays and the methods to investigate the specificity of inhibitors against factor VIII concentrates that may contribute to improve the treatment of hemophilia A patients with inhibitors. Finally, the use and limitations of overall clotting assays, such as clot wave form analysis, thromboelastography, and thrombin generation assay, in the management of hemophilia A patients with inhibitors are discussed.

Keywords: hemophilia A, factor VIII inhibitors, Nijmegen assay, Bethesda assay, epitope specificity
Correspondence: B Verbruggen, Laboratory of Hematology, Department of Laboratory Medicine, Radboud University Nijmegen Medical Center, PO Box 9101, 6500 HB Nijmegen, The Netherlands. Tel: (31)‐243614796; e‐mail: H.Verbruggen@chl.umcn.nl