Hemophilia A: Emicizumab monitoring and impact on coagulation testing

Abstract

Hemophilia A is an X-linked recessive bleeding disorder characterized by absent or ineffective coagulation factor VIII, a condition that could result in a severe and potentially life-threatening bleed. Although the current standard of care involves prophylactic replacement therapy of factor VIII, the development of neutralizing anti-factor VIII alloantibody inhibitors often complicates such therapeutic treatment. Emicizumab (Hemlibra®), a novel recombinant therapeutic agent for patients with hemophilia A, is a humanized asymmetric bispecific IgG4 monoclonal antibody designed to mimic activated factor VIII by bridging factor IXa and factor X thus effecting hemostasis. Importantly, this drug eliminates the need for factor VIII and complications associated with inhibitor generation. Emicizumab has been approved for use in several countries including the United States and Japan for prophylaxis of bleeding episodes in hemophilia A with and without FVIII inhibitors. Therapy is also approved in the European Union for routine prophylaxis of bleeds in hemophilia A with inhibitors or severe hemophilia A without inhibitors. Unfortunately, emicizumab therapy presents unique challenges for routine and specialty coagulation tests currently used to monitor hemophilia A. In this review, hemophilia A is presented, the biochemistry of factor VIII is discussed, and the impact of the therapeutic agent emicizumab is highlighted.

Keywords: Chromogenic substrate assay; Clot waveform assay; Emicizumab; Factor VIII; Global assays; Hemlibra; Hemophilia A; One-stage assay; Thrombin generation assay; Thromboelastography; Whole blood viscoelastic monitoring.