Does Prehospital administration of Tranexamic Acid in Severe Trauma Lead to Better Outcomes?

A recent international multicentric study has found that among adults with major trauma and suspected trauma-induced coagulopathy who were being treated in advanced trauma systems, prehospital administration of tranexamic acid followed by an infusion over 8 hours did not result in a greater number of patients surviving with a favorable functional outcome at 6 months than placebo.

Trauma is the leading cause of death among young people. Most of the preventable deaths are due to bleeding, which can be exacerbated by trauma-induced coagulopathy involving plasmin-mediated fibrinolysis resulting from tissue injury and hemorrhagic shock. Tranexamic acid, an antifibrinolytic drug, might be an effective treatment.

The effect of in-hospital administration of tranexamic acid in patients with trauma has been previously evaluated in the Clinical Randomisation of an Antifibrinolytic in Significant Haemorrhage (CRASH)–2 and CRASH-3 trials. Tranexamic acid, administered within 3 hours after injury, was shown to reduce 28-day mortality among patients with suspected bleeding (CRASH-2 trial) and among patients with mild-to-moderate traumatic brain injury (CRASH-3 trial).

Unlike the CRASH-2 and CRASH-3 trials, subsequent trials of prehospital tranexamic acid therapy in advanced trauma systems did not show benefits in trauma patients with suspected bleeding6 or isolated traumatic brain injury, and another trial showed a dose-dependent increase in thromboembolism with tranexamic acid therapy. Overall, the balance of benefits and risks of tranexamic acid in advanced trauma systems with multiple prehospital and in-hospital hemorrhage control strategies is uncertain

Recently published in NEJM, the Pre-hospital Antifibrinolytics for Traumatic Coagulopathy and Hemorrhage (PATCH-Trauma) trial, an international multicentric trial was undertaken to evaluate the efficacy and safety of tranexamic acid therapy in patients with severe trauma who were at risk for trauma-induced coagulopathy. The hypothesis was that tranexamic acid initiated before hospital admission in advanced trauma systems would result in a greater percentage of patients surviving with a favorable functional outcome at 6 months than placebo.

The researchers found that there was no significant between-group difference in the percentage of patients surviving with a favorable functional outcome at 6 months. In the trial, for every 100 patients assigned to receive tranexamic acid rather than placebo, there were approximately 4 extra patients alive at 6 months; however, approximately 4 extra patients were also categorized as having severe disability.

They studied patients who were treated in advanced trauma systems, and found that the effect of tranexamic acid on early death and death due to bleeding was consistent with that observed in the CRASH-2 trial, which predominantly enrolled patients who were treated in less-developed trauma systems. The effect of tranexamic acid on functional and long-term outcomes was not reported in the CRASH-2 trial, and this trial provides new information on the quality of survival after severe trauma that is treated with tranexamic acid.

Their finding of no between-group difference in survival with a favorable functional outcome at 6 months is consistent with outcomes reported in a previous trial of tranexamic acid in patients with isolated traumatic brain injury.

A concern about tranexamic acid has been the potential risk of thrombotic complications, the prevention of which is a major focus of trauma care. The authors screened inpatients for deep venous thrombosis in the legs and, in contrast to a previous trials, found little evidence that tranexamic acid increased the risk of such events.

The authors concluded that while administration of tranexamic acid was associated with lower early mortality, it did not result in a higher percentage of patients surviving with a favorable functional outcome at 6 months than placebo.

Reference

Prehospital Tranexamic Acid for Severe Trauma The PATCH-Trauma Investigators and the ANZICS Clinical Trials Group June 14, 2023 DOI: 10.1056/NEJMoa2215457