Background: Warfarin inhibits the generation of vitamin K-dependent proteins. Emicizumab can prevent bleeding episodes in persons with hemophilia A (PwHA). The hemostatic potential of emicizumab combined with warfarin in PwHA remains to be clarified. Aim: To assess the coagulation of emicizumab combined with warfarin in a simulated whole blood model of PwHA. Methods: We collect 19 whole blood samples from 10 patients taking warfarin and the prothrombin time-international normalized ratio (PT-INR) was used to defined groups as near-normal (INR 1.2-1.48; n=4), subtherapeutic (INR 1.56-1.9; n=7) and therapeutic (INR > 2.0; n=8). Factor (F)VIII activity (FVIII:C) was neutralized using an anti-FVIII inhibitor antibody (termed FVIII-depleted) prior to the addition of therapeutic concentrations emicizumab (50 µg/mL). Coagulation potential was then measured using Ca 2+-triggered rotational thromboelastometry and compared with that determined in emicizumab-treated PwHA. The FII:C, FVII:C, FIX:C, FX:C, protein C (PC):C, and PS:C levels in warfarin-treated samples were also measured. Results: The average PT-INR in near-normal, subtherapeutic, and therapeutic groups were 1.3±0.1, 1.7±0.1, and 2.4±0.4, respectively, and levels of FII:C, FVII:C, FIX:C, FX:C, PC:C, and PS:C ranged from 50-70%, 35-50%, and 15-35%, 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 the addition of emicizumab in subtherapeutic and therapeutic groups were lower than that in PwHA receiving emicizumab. Conclusion: Concentrations of vitamin K-dependent proteins influence hemostatic function in PwHA receiving emicizumab, and PT-INR monitoring could be informative in these individuals.