Ex vivo analysis of emicizumab activity in murine plasma samples. (A) Plasma samples obtained from FVIII-deficient mice receiving emicizumab combined with human FIX/FX were analyzed for procoagulant activity in a diluted aPTT assay. Clotting times for each emicizumab dose are presented. Data represent mean plus or minus SD of 3 to 9 samples. Clotting times of murine FVIII-deficient plasma, spiked with known FVIII concentrations, are indicated as dotted blue lines for comparison. (B-C) Plasma samples obtained from FVIII-deficient mice receiving emicizumab combined with human FIX/FX (B) or FVIII combined with human FIX/FX (C) were analyzed in a FXIa-induced thrombin-generation assay. Data represent mean of 3 to 5 mice. Thrombin generation in the absence of emicizumab or FVIII (black dotted line) is the same for both panels. Data on lag time, ETP, and thrombin peak are presented in Table 1.