Schematic representation of FVIIa-induced EV release. FVIIa, upon binding to EPCR on endothelial cells, cleaves PAR1 at the canonical R41 cleavage site. This results in the externalization of PS to the outer leaflet of the plasma membrane. FVIIa activation of PAR1 also leads to the budding of EVs from endothelial cells. Thus, FVIIa-induced EVs are enriched with PS and capable of supporting FVIIa-induced hemostasis in hemophilia patients and patients with platelet disorders.