The procoagulant molecule plasminogen activator inhibitor-1 is associated with injury severity and shock in patients with and without traumatic brain injury

BACKGROUND 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. METHODS We retrospectively analyzed demographic, ISS, and hemodynamic data from a prospectively collected database. Patients with traumatic injury requiring intensive care unit admission (n = 268) were classified as multiple injuries, isolated body, or isolated head based on Abbreviated Injury Severity score. Admission PAI-1 levels were quantified using a Luminex analyte platform. Univariate tests for association informed the construction of a multivariate model of the relationship between PAI-1 and ISS. RESULTS Plasminogen activator inhibitor-1 positively associated with ISS (p < 0.0001) and was highest in patients with ISS greater than 35 (p < 0.0001). Plasminogen activator inhibitor-1 was significantly different between multiple injuries, isolated body, and isolated head patients (p < 0.0001). On univariate analysis, age (p = 0.0011), hypotension (p = 0.0076), and alcohol intoxication (p = 0.0024) were all positively associated with PAI-1 level. Admission international normalized ratio was not associated with PAI-1 level (p = 0.638). After adjusting for age, sex, hypotension, and alcohol intoxication, higher PAI-1 levels were associated with higher ISS (p < 0.0001). CONCLUSION Elevated PAI-1 at admission is associated with higher ISS. This association is more pronounced in patients with hypotension. These findings suggest that PAI-1 levels may reflect the burden of endothelial damage and platelet activation after injury. LEVEL OF EVIDENCE Prognostic, level III.