Table 1.

Potential mechanisms by which VWF contributes to TBI-induced coagulation abnormalities

ULVWF functions as an adhesive ligand to mediate the interaction between pathologic BDEVs and endothelial cells. BDEVs with exposed phosphatidylserine bind coagulation factors, leading to a consumptive coagulopathy.

ULVWF anchors to endothelial cells and tethers platelets, leukocytes and EVs to the endothelium, worsening inflammatory injury and serving as a nidus for microvascular thromboses.

ULVWF released from injured endothelial cells overwhelms the cleavage capabilities of ADAMTS13, resulting in accumulation of uncleaved hyperadhesive VWF in circulation which then activate platelets and occludes the microvasculature.

VWF indicates von Willebrand factor; ULVWF, ultra-large VWF; BDEVs, brain-derived extracellular vesicles.