Prehospital tranexamic acid is associated with a dose-dependent decrease in syndecan-1 after trauma: A secondary analysis of a prospective randomized trial

BACKGROUND: In the Study of Tranexamic Acid During Air and Ground Prehospital Transport (STAAMP) Trial, prehospital tranexamic acid (TXA) was associated with lower mortality in specific patient subgroups. The underlying mechanisms responsible for a TXA benefit remain incompletely characterized. We hypothesized that TXA may mitigate endothelial injury and sought to assess whether TXA was associated with decreased endothelial or tissue damage markers among all patients enrolled in the STAAMP Trial. METHODS: We collected blood samples from STAAMP Trial patients and measured markers of endothelial function and tissue damage including syndecan-1, soluble thrombomodulin (sTM), and platelet endothelial cell adhesion molecule-1 at hospital admission (0 hours) and 12 hours, 24 hours, and 72 hours after admission. We compared these marker values for patients in each treatment group during the first 72 hours, and modeled the relationship between TXA and marker concentration using regression analysis to control for potential confounding factors. RESULTS: We analyzed samples from 766 patients: 383 placebo, 130 abbreviated dosing, 119 standard dosing, and 130 repeat dosing. Lower levels of syndecan-1, TM, and platelet endothelial cell adhesion molecule measured within the first 72 hours of hospital admission were associated with survival at 30 days (p < 0.001). At hospital admission, syndecan-1 was lower in the TXA group (28.30 [20.05, 42.75] vs. 33.50 [23.00, 54.00] p = 0.001) even after controlling for patient, injury, and prehospital factors (p = 0.001). For every 1 g increase in TXA administered over the first 8 hours of prehospital transport and hospital admission, there was a 4-ng/mL decrease in syndecan-1 at 12 hours controlling for patient, injury, and treatment factors (p = 0.03). CONCLUSION: Prehospital TXA was associated with decreased syndecan-1 at hospital admission. Syndecan-1 measured 12 hours after admission was inversely related to the dose of TXA received. Early prehospital and in-hospital TXA may decrease endothelial glycocalyx damage or upregulate vascular repair mechanisms in a dose-dependent fashion. LEVEL OF EVIDENCE: Therapeutic/Care Management; Level III.