ANV-6L15 blocked the assembly of extrinsic tenase complexes on EVs. (A) Time-dependent changes in the circulating EVs in peripheral blood samples from TBI mice (n = 9 mice per group, 1-way ANOVA; *P < .05; BDEVs vs pEVs and eEVs, no statistical difference between pEVs, and eEVs). (B) ANV-6L15-bound EVs concentrated from TBI mice and BDEVs made in vitro were detected by immunoblots (representative of 3 separate experiments). (C) ANV-6L15 bound more BDEVs than did heterogeneous EVs from TBI mice (n = 10 mice per group, Student t test). (D) ANV-6L15-bound EVs concentrated from TBI and sham mice in a dose-dependent fashion (detected by a FITC-anti-ANV antibody, n = 9 mice per group, 1-way ANOVA; *P < .001; **P < .01 vs untreated). (E-G) FVII (E), FXa (F), and fibrinogen (G) were detected on the surfaces of EVs from TBI mice, with the highest levels found on BDEVs. ANV-6L15 reduced the formation of the tenase complex (n = 9 mice per group, Kruskal-Wallis 1-way ANOVA on ranks).