SR604 restores hemostasis by selectively blocking APC anticoagulant activity. The anti-APC mAb SR604 binds with ultra-high affinity to APC at an epitope important for binding to its substrate, FVa. In doing so, it potently blocks APC anticoagulant activity to restore thrombin generation in preclinical hemophilia models. In contrast, SR604 does not impede endogenous APC anti-inflammatory activity via PAR1.