Abstract
Traumatic brain injury (TBI) is a leading cause of death and disability. Patients with isolated TBI lose a limited amount of blood to primary injury, but they often develop secondary coagulopathy, resulting in delayed or recurrent intracranial and intracerebral hematoma. TBI-induced coagulopathy is closely associated with poor outcomes for these patients, including death. This secondary coagulopathy is consumptive in nature, involving not only brain-derived molecules, coagulation factors, and platelets, but also endothelial cells in a complex process now called blood failture. A key question is how a localized injury to the brain is rapidly disseminated to affect systemic hemostasis that is not directly affected the way it is in trauma to the body and limbs, especially with hemorrhagic shock. Increasing evidence suggests that the adhesive ligand von Willebrand factor (VWF), which is synthesized in and released from endothelial cells, plays a paradoxical role in both facilitating local hemostasis at the site of injury and also propagating TBI-induced endotheliopathy and coagulopathy systemically. This review discusses recent progress in understanding these diverse activities of VWF and the knowledge gaps in defining their roles in TBI and associated coagulopathy.