A hypercoagulable state was induced primarily by EVs in TBI mice and reversed by ANV-6L15. (A) Blood samples from experimental mice were processed to generate PPP, concentrated EVs, and EV-free plasma (EVFP) and tested for thrombin generation (n = 7 mice per group, 1-way ANOVA). (B) Plasma levels of EVs that bound ANV in TBI and sham mice (n = 10 mice per group, Student t test). (C) BDEVs promoted thrombin generation in a dose-dependent fashion. The graph shows thrombin generation profiles, and the bar-graph insert summarizes the results of 12 independent experiments (1-way ANOVA; *P < .01 vs normal plasma). (D) Thrombin generation induced by 3 × 10⁴/µL of BDEVs was blocked by ANV-6L15 in a dose-dependent manner. The bar-graph insert summarizes the results of 12 independent experiments (1-way ANOVA; *P < .01 vs normal plasma). Plasma levels of EVs from the brains (BDEV, using glial cell EVs [GFAP⁺] as the surrogate marker), eEVs, and pEVs (E) as well as leuEVs (F) in sham mice and TBI mice receiving ANV-6L15 or an equal volume of the vehicle buffer (n = 7 mice per group, 1-way ANOVA).