| Autor: |
Mancazzo, Federica, Vitulli, Antonia, Dirienzo, Lavinia, Ammollo, Concetta T., Semeraro, Fabrizio, Colucci, Mario |
| Předmět: |
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| Zdroj: |
Bleeding, Thrombosis & Vascular Biology; 2023, Vol. 2 Issue 4, p1-7, 7p |
| Abstrakt: |
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 emicizumabplasma 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. [ABSTRACT FROM AUTHOR] |
| Databáze: |
Complementary Index |
| Externí odkaz: |
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