Influence of emicizumab on protein C-mediated clotting regulation

Submitted: 20 July 2023
Accepted: 21 September 2023
Published: 25 October 2023
Abstract Views: 1805
PDF: 184
Supplementary Material: 33
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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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Citations

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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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