Overview of the pathway for VWF and brain-derived microparticle-induced vascular leakage and coagulopathy with reversal by ADAMTS-13. Following TBI, mivrovesicles are released from the injured brain and bind to hyperreactive VWF released from endothelial cells. In the presence of activated platelets, VWF-bound microvesicles result in vascular leakage, coagulopathy, and neurological dysfunction. These pathologic processes can be reversed by either ADAMTS-13, which blocks VWF reactivity, or lactadherin, which promotes clearance of the microvesicles.