Use of SerpinPC to treat an ongoing bleed in HA mice and in WT mice treated with apixaban. (A) Mice were cannulated via the jugular vein to allow for the administration of agent 1 minute after tail transection. Vehicle-treated background control (B6;129S) mice (magenta) and HA mice (red) gave blood loss values similar to those observed in the pretreatment model. Human fVIII at 100 and 400 U/kg (green) and NovoSeven at 90 and 270 μg/kg (orange) reduced blood loss volume in a dose-dependent manner. SerpinPC reduced blood loss volume at doses of 1, 10, and 100 mg/kg (blue), with maximal effect observed for the 2 higher doses. Four mice were used per group, with median indicated. (B) To assess the ability of SerpinPC to reduce excessive bleeding caused by overanticoagulation, WT B6;129S mice were treated with either vehicle (magenta) or 10 mg/kg apixaban via jugular vein cannulas 5 minutes before tail transection. One minute after tail transection, either vehicle (red), 100 IU/kg Factor Eight Inhibitor Bypassing Agent (FEIBA; yellow), or 10 mg/kg SerpinPC (blue) was administered via the jugular vein, and bleeding volume was assessed over 20 minutes (n = 6 per group with averages indicated).