In vitro evaluation of global coagulation potential of emicizumab and warfarin using rotational thromboelastometry

Warfarin inhibits the generation of vitamin K-dependent proteins and emicizumab can prevent bleeding episodes in people with hemophilia A (PwHA), but their combined hemostatic potential remains unclear. We analyzed the coagulation potential of emicizumab combined with warfarin in a simulated model of PwHA. Nineteen samples were collected from ten patients taking warfarin, and the prothrombin time-international normalized ratio (PT-INR) was used to define near-normal (INR 1.2-1.48; n = 4), subtherapeutic (INR 1.56-1.9; n = 7) and therapeutic (INR > 2.0; n = 8) groups. Factor (F)VIII activity (FVIII:C) was neutralized using an anti-FVIII inhibitor antibody (termed FVIII-depleted) before the addition of emicizumab (50 µg/mL). Coagulation potential was measured using Ca2 + -triggered rotational thromboelastometry, and was compared with that in emicizumab-treated PwHA. The average PT-INR in the near-normal, subtherapeutic, and therapeutic groups was 1.3 ± 0.1, 1.7 ± 0.1, and 2.4 ± 0.3, respectively. The hemostatic potential in FVIII-depleted samples mixed with emicizumab in the near-normal group was comparable to that in emicizumab-treated PwHA. The coagulation potential in FVIII-depleted samples after addition of emicizumab in the subtherapeutic and therapeutic groups were lower than that in emicizumab-treated PwHA. PT-INR monitoring could be informative in emicizumab-treated PwHA due to the influence of vitamin K-dependent proteins.