Figure 1.
Inhibition of DOAC-induced bleeding by superFVa and an anti-protein C antibody. Mice were treated with apixaban (8 mg/kg) (A), rivaroxaban (40 mg/kg) (B), or dabigatran (0.4 mg/kg) (C) by IV tail vein injection and bleeding was measured for 20 minutes after tail clip. Blood loss was expressed in microliters of blood per gram (g) mouse. (D) Human plasma with and without apixaban, rivaroxaban (both 200 nM) or dabigatran (1 μM) were treated with superFVa (100 nM) and endogenous thrombin potential was assessed. (E) Mice were injected retro-orbitally with the blocking anti-protein C and APC [(A)PC] antibody SPC-54 (5 mg/kg) 2 hours before IV treatment with apixaban (8 mg/kg), rivaroxaban (40 mg/kg), or dabigatran (0.4 mg/kg). Bleeding was measured for 20 minutes after tail clip. Blood loss was expressed in microliters of blood per gram (g) mouse. Error bars represent SEM (n = 7-14 per group). P values were determined by Kruskal-Wallis followed by a 2-tailed Mann-Whitney U test and values ≤.05 were considered statistically significant.