The potential role of emicizumab prophylaxis in severe von Willebrand disease

Authors: Barg, AA., Avishai, E., Budnik, I., Brutman, TB., Tamarin, I., Dardik, R., Bashari, D., Misgav, M., Lubetsky, A., Lalezari, S., Livnat, T., and Kenet, G.

Publication: Blood Cells, Molecules, and Diseases; 87,102530Blood Cells, Molecules, and Diseases; January 2021

Affiliations: National Hemophilia Center, Sheba Medical center, Tel Hashomer, Israel; Amalia Biron Research Institute of Thrombosis and Hemostasis, Sackler School of Medicine, Tel Aviv University, Israel; Department of Pathophysiology, Sechenov First Moscow State Medical University (Sechenov University), Moscow, Russia.

Abstract: BACKGROUND: Severe von Willebrand disease (VWD) may be associated with chronic joint damage and may require prophylactic therapy. Emicizumab is a humanized bispecific antibody, which mimics the function of coagulation factor VIII (FVIII), and it has been approved for prophylaxis in hemophilia A. METHODS: This is the first study assessing the potential future role of emicizumab as an alternative prophylactic treatment in patients with severe VWD, based upon a thrombin generation (TG) ex vivo analysis. We report 51 weeks of successful off label emicizumab prophylaxis in a child with severe VWD and recurrent hemarthroses and progressive arthropathy despite adherence to previous prophylaxis with replacement therapy. RESULTS AND CONCLUSIONS: Our work demonstrated that ex vivo spiking with emicizumab increased TG in plasma from patients with type 3 VWD. Similar TG results were observed in our treated patient, whose therapy was well tolerated without any adverse events. Both in vitro and ex vivo TG data support sufficient hemostasis without exceeding the range seen in healthy volunteers. Further collaborative studies on the efficacy and safety of emicizumab prophylaxis in severe VWD is warranted.