Combined activity of FVIII and emicizumab. (A) Emicizumab (3 mg/kg given 24 hours before tail bleeding) and FVIII (5 or 7.5 U/kg given 5 minutes before tail bleeding) were given separately or in combination together with human FIX/FX (100 U/kg) to FVIII-deficient mice as described for Figures 3 and 4. Each data point represents an individual mouse. Data for FVIII without emicizumab are similar to those presented in Figure 3A, and data for emicizumab without FVIII are similar to those presented in Figure 4B. Statistical analysis was performed via 1-way ANOVA with Tukey multiple comparison. Data of mice receiving only FIX/FX (but no emicizumab or FVIII) are similar as those presented in Figure 3A. (B) FXIa-induced thrombin generation of human FVIII-deficient plasma (orange), which was spiked with emicizumab (20 μg/mL; blue), FVIII (10 U/dL; green), or both in the absence (red) or presence (black dotted line) of recombinant murine FIX (mFIX; 100 U/dL). Thrombogram is representative for 3 independent experiments. NS, not significant.