Original Articles
25 October 2023
Vol. 2 No. 4 (2023)
https://doi.org/10.4081/btvb.2023.89

Influence of emicizumab on protein C-mediated clotting regulation

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Emicizumab, protein C resistance, intrinsic pathway, thrombotic risk
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Federica Mancazzo
Department of Precision and Regenerative Medicine and Ionian Area, Aldo Moro University, Bari, Italy.
Antonia Vitulli
Department of Precision and Regenerative Medicine and Ionian Area, Aldo Moro University, Bari, Italy.
Lavinia Dirienzo
Department of Precision and Regenerative Medicine and Ionian Area, Aldo Moro University, Bari, Italy.
Concetta T. Ammollo
Department of Precision and Regenerative Medicine and Ionian Area, Aldo Moro University, Bari, Italy.
Fabrizio Semeraro
Department of Precision and Regenerative Medicine and Ionian Area, Aldo Moro University, Bari, Italy.
Mario Colucci
mario.colucci@uniba.it
https://orcid.org/0000-0001-9146-8095
Department of Precision and Regenerative Medicine and Ionian Area, Aldo Moro University, Bari, Italy.

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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Influence of emicizumab on protein C-mediated clotting regulation. (2023). Bleeding, Thrombosis and Vascular Biology, 2(4). https://doi.org/10.4081/btvb.2023.89
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