https://doi.org/10.4081/btvb.2023.89
Influence of emicizumab on protein C-mediated clotting regulation
Submitted: 20 July 2023
Accepted: 21 September 2023
Published: 25 October 2023
Accepted: 21 September 2023
Abstract Views: 1833
PDF: 186
Supplementary Material: 34
Supplementary Material: 34
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All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.
Authors
Emicizumab, a FVIII-mimetic bispecific antibody, is insensitive to degradation by activated protein C (APC) and may thus induce a procoagulant state. We investigated the effect of emicizumab on protein C-mediated inhibition of coagulation under in vitro conditions mimicking physiological and pathological clotting activation. Thrombin generation (TG) in tissue factor-triggered hemophilic plasma containing emicizumab (50 μg/mL) was inhibited by APC or thrombomodulin in a concentration-dependent manner, and to a similar extent as in plasma added with FVIII (Kovaltry, 1 IU/mL). However, when clotting was activated via the intrinsic pathway, emicizumab-plasma displayed resistance to APC, manifested by a barely detectable prolongation of the lag time of TG, and by the lack of inhibition of FXa generation. Moreover, in contact-activated plasma added with APC, the generation of a second wave of thrombin, following prothrombin replenishment, was much greater in emicizumab-plasma than in Kovaltry-plasma, suggesting that the insensitivity of emicizumab to APC may translate in greater thrombin formation. Considering the major role played by the contact system in the thrombotic process, hemophilia A patients under emicizumab treatment might be at increased thrombotic risk.
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How to Cite
Mancazzo, F., Vitulli, A., Dirienzo, L., Ammollo, C. T., Semeraro, F., & Colucci, M. (2023). Influence of emicizumab on protein C-mediated clotting regulation. Bleeding, Thrombosis and Vascular Biology, 2(4). https://doi.org/10.4081/btvb.2023.89
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