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

Condron, Mary MD; Rowell, Susan MD; Dewey, Elizabeth MS; Anderson, Taylor; Lealiiee, Lelani; Farrell, David PhD; Hinson, Holly MD, MCR

Journal of Trauma and Acute Care Surgery: November 2018 - Volume 85 - Issue 5 - p 888–893
doi: 10.1097/TA.0000000000002040

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.

From the Division of Trauma, Critical Care & Acute Care Surgery (M.C., S.R., E.D., T.A., L.L., D.F., H.H.), Oregon Health & Science University, Portland, Oregon.

Submitted: January 14, 2018, Revised: July 4, 2018, Accepted: July 18, 2018, Published online: August 6, 2018.

Presented at the 48th Annual Meeting of the Western Trauma Association, February 26, 2018 in Whistler, British Columbia.

Address for reprints: Mary Condron, MD, Division of Trauma, Critical Care & Acute Care Surgery, Oregon Health & Science University, 3181 SW Sam Jackson Park Rd, L611, Portland, OR 97239; email:

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© 2018 Lippincott Williams & Wilkins, Inc.