Research enabled by the emicizumab-adapted hemophilia A mouse bleeding model. Emicizumab (Hemlibra, also known as ACE910) is a FVIIIa mimetic that changes the familiar coagulation dynamics of FVIII replacement in hemophilia A since it is not based on FVIII. Instead, the activity of Emicizumab is regulated by the generation of FIXa and the formation of the heterodimeric FIX(a)-emicizumab-FX complex, while traditional regulation of FVIIIa by spontaneous inactivation and proteolytic inactivation by activated protein C (APC) are no longer applicable. This change in coagulation dynamics has several implications in hemophilia for the reduction of bleeding, the activity of other bypassing agents, and possibly the concentration of FVIII required for immune tolerance induction (ITI) and progression of hemophilic arthropathy (see text for details). The emicizumab-adapted hemophilia A mouse bleeding model, using human FIX (+hFIX) and FX (+hFX), enables comparison of the effects of emicizumab to that of FVIII to improve our understanding of the mechanisms and regulation of prohemostatic effects of emicizumab.