Trending Topics

Research Analysis: Prehospital tranexamic acid for severe trauma

What does the latest study mean for prehospital use of TXA?


Photo/Ray Kemp

Research study: The PATCH-Trauma Investigators and the ANZICS Clinical Trials Group. Prehospital tranexamic acid for severe trauma. N Engl J Med. DOI: 10.1056/NEJMoa2215457(1)

The population. 1,310 adult patients with severe trauma assessed to be at risk of trauma induced coagulopathy (COAST score >2) were recruited by 15 EMS services (Australia, Germany and New Zealand) and randomly assigned (1:1) to the intervention group or the comparator group. Exclusion criteria included known/suspected pregnancy or resident of a facility for older persons. Three patients were lost due to errors in randomization.

The coagulopathy of severe trauma score [2]


The intervention. The experimental group (661 patients) received tranexamic acid 1 gm IV, followed by 1 gm over 8 hours.

The comparator. The control group (646 patients) received a placebo.

The outcome. The purpose was to compare the safety and effectiveness of both head-to-head. The primary outcome was survival with a favourable neurological outcome at 6 months. Secondary outcomes include death within 24 hours, death within 28 days and death within 6 months.


Favourable outcome at 6 months had no significant difference between TXA and placebo – 53.7% (307/572) vs. 53.5% (299/559); absolute risk difference, 0.2 percentage points; 95% confidence interval [CI], -5.6 to 6.0; risk ratio, 1.00; 95% CI, 0.90 to 0.12 (42.9% vs 18.2%, RR 0.42, 95% CI 0.22-0.80; p=0.0007)

Screenshot 2023-06-20 at 4.05.39 PM.png

TXA is an antifibrinolytic agent. Conceptually, the body’s fibrinolytic mechanism can get bumped into overdrive by things like trauma, resulting in coagulopathy. The use of TXA has been hypothesized to help reduce the incidence of trauma-induced coagulopathy, which, along with hypothermia and acidosis, represents the trauma triad; thought to be responsible for much of the correctable mortality in severe injury. Support for the use of TXA in trauma primarily comes from the CRASH-2 study. Other research presents conflicting arguments regarding the value of TXA in hemorrhage. The PATCH study attempts to address several limitations of the CRASH-2 study, specifically, prehospital administration of TXA, in an advanced system and using 6 month favourable outcomes as opposed to 28 day mortality as a primary endpoint.


Methodologically, the study is sound. It was blinded and placebo controlled experimental research, with sufficient numbers to make the primary outcome significant. Losses to protocol violations, follow-up and incomplete data are to be expected in the less controlled prehospital environment. These were accounted for, and the authors used an intention-to-treat analysis. This more conservative approach to analysis helps to avoid bias by including everyone who was enrolled, regardless of whether they complete the protocol.

The study is relevant for a number of reasons. It supports previous literature (from CRASH-2) that TXA improves mortality at 24 hours (9.7% vs 14.7%) and 28 days (17.3% vs 21.8%) after injury. The study adds to the literature in two important ways.

  1. First, it is experimental research involving TXA in the prehospital environment, something that has been lacking.
  2. Second, it studied more meaningful outcomes for both patients and families, evaluating both the longer term impact of TXA (6 months versus 28 days) as well as using favourable neurological outcome instead of mortality.

This study does demonstrate a trend towards benefit from TXA in youngers patients (<50 years old), with earlier administration (<2 hours), in penetrating trauma and in patients with GCS <9. Importantly, the study was not powered to answer these questions, so these findings should be considered as direction for further research, not practice changing.


“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.”

“… our data do not preclude the possibility that tranexamic acid can prevent early death from bleeding in some patients who will go on to make a good recovery.”

“… in contrast to a previous trial of tranexamic acid in major trauma patients and another trial of tranexamic acid in nontraumatic gastrointestinal bleeding, found little evidence that tranexamic acid increased the risk of such events (venous thrombosis).”


This study does not support any change in current practice with respect to prehospital TXA in trauma. It showed improved 24-hour and 28-day mortality, findings which are consistent with CRASH-2. It provides new information demonstrating no difference in favourable neurological outcome at 6 months. This leaves two major questions unanswered. First, does TXA reduce mortality but leave patients with severe neurological impairment? Or do patients receiving TXA simply take longer than 6 months to recover? Second, should we be more selective in the patients who receive TXA (targeting younger patients or penetrating trauma)?


Read next:

Understanding TXA

What does the evidence really say about prehospital TXA


  1. The PATCH-Trauma Investigators and the ANZICS Clinical Trials Group. Prehospital tranexamic acid for severe trauma. N Engl J Med. DOI: 10.1056/NEJMoa221545
  2. Mitra, B., Bernard, S., Gantner, D., Burns, B., Reade, M.C., Murray, L., Trapani, T., Pitt, V., McArthur, C., Forbes, A. and Maegele, M., 2021. Protocol for a multicentre prehospital randomised controlled trial investigating tranexamic acid in severe trauma: the PATCH-Trauma trial. BMJ open, 11(3), p.e046522.
  3. CRASH-2 trial collaborators; Shakur H, Roberts I, Bautista R, Caballero J, Coats T, Dewan Y, El-Sayed H, Gogichaishvili T, Gupta S, Herrera J, Hunt B, Iribhogbe P, Izurieta M, Khamis H, Komolafe E, Marrero MA, Mejía-Mantilla J, Miranda J, Morales C, Olaomi O, Olldashi F, Perel P, Peto R, Ramana PV, Ravi RR, Yutthakasemsunt S. Effects of tranexamic acid on death, vascular occlusive events, and blood transfusion in trauma patients with significant haemorrhage (CRASH-2): a randomised, placebo-controlled trial. Lancet. 2010 Jul 3;376(9734):23-32. doi: 10.1016/S0140-6736(10)60835-5. Epub 2010 Jun 14. PMID: 20554319.

Jonathan Lee is a critical care paramedic with Ornge in Toronto, Canada, with over 25 years of experience in 911, critical care, aeromedical and pediatric critical care transport. Jonathan’s teaching experience includes classroom, clinical and field education as well as curriculum development and design across a number of health professions.

He is currently delivering KinderMedic, a program he developed to improve the confidence and competence of prehospital providers caring for acutely ill children. In addition to his clinical practice, he is also adjunct faculty in the Paramedic Program at Georgian College. Jonathan is a freelance author and has been invited to speak across North America and Europe on topics such as pediatrics, analgesia and stress.

Jonathan has previously served on committees for professional organizations including the Ontario Paramedic Association and NAEMT. He is currently pursuing a Master of Science in Critical Care from Cardiff University. Jonathan can be contacted via Twitter and LinkedIn.