Tranexamic acid did not attenuate the acute rise in plasma syndecan-1 in a severely injured cohort: a laboratory analysis of the PATCH clinical trial

Abstract

Background: Injury to the vascular endothelium occurs in up to 34% of patients acutely following severe traumatic injury and can be quantified clinically by measuring the plasma concentration of syndecan-1 (SDC-1). Tranexamic acid (TXA) attenuates endothelial damage in animal and cell culture models and has been associated with lower SDC-1 levels after prehospital TXA administration. The aim of this study was to assess the association of prehospital TXA on SDC-1 levels in a more severely injured prehospital cohort. Methods: The PATCH-Trauma trial randomised patients to receive pre-hospital TXA or placebo. In this sub-cohort, SDC-1 was measured in blood samples collected on hospital admission, at 8 and 24 h. Relationships between SDC-1 levels over time, treatment groups, and outcomes were analyzed using regression modelling controlling for potential confounding factors. Results: There were 89 patients included, with 57 administered TXA and 32 administered placebo (per protocol). SDC-1 levels were available in 87 patients on arrival to hospital, 70 at 8 h, and 69 at 24 h. Patients had a median SDC-1 on admission of 106 ng/mL (IQR 88–137). There was no effect of TXA treatment on SDC-1 levels over the first 24 h of hospital admission, even after controlling for known confounders. There was no association between SDC-1 level at any time point and the development of deep vein thrombosis or sepsis, mortality at 28-days, or days alive and out of hospital, even after adjustment for confounding factors. Conclusion: Administration of TXA, initiated pre-hospital, did not affect SDC-1 levels in the first 24 h of hospital admission in this severely injured cohort. Further research is required to elucidate the mechanisms of the effect of TXA on the endothelium as well as the utility of SDC-1 as an endothelial biomarker.