Schematic pathways for consumptive coagulopathy induced by TBI. (A) Hemostasis is triggered by platelet adhesion and aggregation at the site of vascular injury and stabilized by crosslinked fibrin polymers to form a hemostatic plug. (B) The tissue factor and anionic phospholipid-rich microvesicles (BDMVs and exMTs) from injured brain cells are released into the circulation to provide microplatforms for tenase assembly. Thrombin thus produced (1) cleaves fibrinogen to generate fibrin, (2) activates platelets, and (3) activates endothelial cells to generate platelet and endothelial cell MVs. The blood cell–derived MVs further amplify the coagulation initiated by BDMVs and exMTs. Endothelial cells activated by MVs, thrombin, and fibrin also induce the acute release of tPA, which initiates early fibrinolysis. All of these processes occur in the fluid phase of the blood, without the local vascular injury and blood-derived factors found in trauma patients with hemorrhagic shock. EC, endothelial cells; FVa, activated factor V; FVII, coagulation factor VII; FXa, activated factor X; PS, phosphatidylserine; TF, tissue factor.