In vivo dose response of FVIII in FVIII-deficient mice. (A) FVIII-deficient mice received a mixture of FVIII (0-10 U/kg), human FIX (100 U/kg), and human FX (100 U/kg) via retro-orbital infusion. Five minutes after infusion, the terminal 3 mm of the tail was amputated, and shed blood was collected for 30 minutes. Presented is blood loss over 30 minutes vs FVIII dose. Each data point represents an individual mouse. Statistical analysis was performed via 1-way ANOVA with Dunnett multiple comparison. (B) Data presented in panel A but depicted as mean plus or minus SD (n = 6-9; blue symbols). A similar dose-response curve was generated in the absence of human FIX and FX (n = 6 per dose; red symbols). ED₅₀, half-maximal effective dose.