Early Tranexamic Acid Administration After Traumatic Brain Injury Is Associated With Reduced Syndecan-1 and Angiopoietin-2 in Patients With Traumatic Intracranial Hemorrhage.

Abstract

To evaluate the effect of early tranexamic acid (TXA) administration on circulating markers of endotheliopathy. Twenty trauma centers in the United States and Canada. Patients with moderate-to-severe traumatic brain injury (TBI) (MS-TBI) and intracranial hemorrhage who were not in shock (systolic blood pressure ≥90 mm Hg). TXA (2 g) or placebo administered prior to hospital arrival, less than 2 hours postinjury. Blood samples and head computed tomographic scan collected upon arrival. Plasma markers measured using Luminex analyte platform. Differences in median marker levels evaluated using t tests performed on log-transformed variables. Comparison groups were TXA versus placebo and less than 45 minutes versus 45 minutes or more from time of injury to treatment administration. Plasma levels of angiopoietin-1, angiopoietin-2, syndecan-1, thrombomodulin, thrombospondin-2, intercellular adhesion molecule 1, vascular adhesion molecule 1. Demographics and Injury Severity Score were similar between the placebo (n = 129) and TXA (n = 158) groups. Levels of syndecan-1 were lower in the TXA group (median [interquartile range or IQR] = 254.6 pg/mL [200.7-322.0] vs 272.4 pg/mL [219.7-373.1], P = .05. Patients who received TXA less than 45 minutes postinjury had significantly lower levels of angiopoietin-2 (median [IQR] = 144.3 pg/mL [94.0-174.3] vs 154.6 pg/mL [110.4-209.8], P = .05). No differences were observed in remaining markers. TXA may inhibit early upregulation of syndecan-1 and angiopoietin-2 in patients with MS-TBI, suggesting attenuation of protease-mediated vascular glycocalyx breakdown. The findings of this exploratory analysis should be considered preliminary and require confirmation in future studies.