: Complete plasminogen activator inhibitor-1 (PAI-1) deficiency is a very rare genetic disorder that is associated with an increased risk of bleeding diathesis.
A profibrinolytic coagulopathy phenotype was demonstrated in all subgroups with increased tissue plasminogen activator levels and decreased plasminogen activator inhibitor-1 levels.
Traumatic injury is associated with an increased risk of coagulopathy and venous thrombosis. plasminogen activator inhibitor-1 (PAI-1) is a procoagulant molecule that inhibits tPA/uPA, thrombomodulin, and activated protein C. We hypothesized that elevated PAI-1 levels would be associated with increased Injury Severity Score (ISS) in injured patients with and without traumatic brain injury and that PAI-1 levels would vary with injury type.
Using a murine model of severe TBI, we found that ICH is reduced in tPA(-/-) and uPA(-/-) mice but increased in PAI-1(-/-) mice compared with wild-type (WT) mice. tPA(-/-), but not uPA(-/-), mice developed a systemic coagulopathy post-TBI.