Age matters: A Secondary Analysis of Endothelial Biomarkers in the Prehospital Tranexamic Acid for Traumatic Brain Injury Trial

BACKGROUND Injured older adults account for nearly 25% of trauma admissions nationwide with increased morbidity and mortality compared with younger adults. Endothelial dysfunction has been associated with poor outcomes in trauma patients. We hypothesized that posttraumatic endothelial changes in older versus younger adult trauma patients will be different with worse outcomes in older adults. METHODS This is a retrospective secondary analysis of the "Tranexamic Acid (TXA) in Traumatic Brain Injury"prehospital database (2015-2017). We studied patients with admission endothelial biomarkers: intercellular adhesion molecule 1, angiotensin 1, thrombomodulin, vascular cell adhesion molecule 1 (VCAM 1), angiotensin 2, syndecan-1, and thrombospondin. We divided patients into age quartiles and compared the oldest quartile (older age [OA] group) with the three youngest quartiles (younger age [YA] group). In-hospital, discharge, and mortality outcomes were compared. Significance was set at p < 0.05. RESULTS A total of 436 patients were included. The mean age in OA group was 66 years (55-88 years, n = 108). The YA mean age was 30 years (15-54 years, n = 328). There was no difference between OA and YA in rates of blunt trauma (98.1% vs. 96.3%, p = 0.61), head abbreviated injury scale (mean, 2.83 vs. 2.93; p = 0.582), or Injury Severity Score (mean, 21 vs. 19; p = 0.29). Tranexamic acid dosing was not different between cohorts (p = 0.571). Overall, the OA group had higher thrombomodulin (median, 693.3 vs. 592.9 pg/mL; p = 0.0008), VCAM 1 (median, 70,852 vs. 59,738 pg/mL; p = 0.0015), and angiotensin 2 (median, 165.3 vs. 134.2 pg/mL; p = 0.005). When comparing endothelial biomarkers of OA to each YA age quartile subsets, in the 2g TXA group OA patients had significantly higher syndecan-1 levels from a subset of YA (37 to 54-year-olds, p = 0.034). In the 2g TXA group OA patients had significantly lower plasma thrombomodulin, angiotensin 2, and VCAM 1 (p = 0.00001, p = 0.0032, and p = 0.0002, respectively) than patients in the placebo group. None of the biomarkers were independent predictors of 28-day mortality. CONCLUSION Despite similar injury patterns, OA presented with higher admission endothelial plasma biomarkers. The OA patients receiving 2 g of TXA had significantly different endothelial biomarker levels versus YA group. These differences suggest that OA patients have a different baseline endothelial function prior to injury and that TXA may have a more pronounced effect on injured OA versus YA endothelium. LEVEL OF EVIDENCE Therapeutic Care Management; Level IV.