Pathogenicity of anti-C1 mAbs in a murine hemophilia A bleeding model. (A) E16 hemophilia A mice received injections of 0.5 mg/kg (65 nM) anti-C1 mAbs or normal saline as controls followed by 180 U/kg (2.5 nM) BDD fVIII 15 minutes later. Tails snips were performed 2 hours after BDD fVIII injections. Median blood loss per gram of mouse body weight compared with fVIII alone is represented (n = 8-9 mice per group; *P < .05, **P < .01, ***P < .001, ns not significant, Mann-Whitney U test). (B) fVIII antigen and (C) fVIII activity at 2 hours following BDD fVIII injection in the presence or absence of anti-C1 mAbs is shown. Data are presented as mean ± standard error of the mean for fVIII antigen and mean ± SD for fVIII activity (n = 5-8 mice per group; *P < .05, **P < .01, ***P < .001, ns, not significant, Mann-Whitney U test). fVIII activity data are normalized to normal saline only control cohort due to background fVIII activity of 0.38 U/mL in mouse plasmas (data not shown).