TXA in Trauma: An Overview and Applications

Special Insights

Written by:

Hannah Austin, PharmD

Reviewed by Cheryl Wood, PharmD, BCCCP

Trauma is a leading cause of preventable mortality worldwide, and hemorrhage is responsible for many early deaths.¹

Tranexamic acid (TXA), an antifibrinolytic agent that inhibits the conversion of plasminogen to plasmin, has gained widespread attention as a mortality‑reducing intervention in traumatic hemorrhage.²

Its use remains controversial due to variable trial results and concerns regarding timing, safety, and appropriate patient selection, yet it has been incorporated into many trauma protocols.

This article aims to summarize the most influential modern clinical trials supporting TXA use in trauma.

Trauma‑induced coagulopathy (TIC) encompasses a spectrum of coagulation abnormalities that occur following traumatic injury.

Coagulopathy, hypothermia, and acidosis form a “lethal triad” often accentuated by mechanisms including tissue injury and shock provoking endothelial, immune system, platelet, and clotting activation.

Early TIC generally occurs within 6 hours of injury and is characterized by hypocoagulopathy, an inability to achieve hemostasis that can lead to shock and uncontrolled hemorrhaging. Early TIC is often driven by excessive fibrinolysis mediated by tissue plasminogen activator (tPA), accelerating clot breakdown and worsening hemorrhage. TXA directly targets this mechanism, stabilizing clot formation during the critical early phase.

Late TIC usually occurs more than 24 hours after injury and is represented by hypercoagulopathy, where excessive macro‑clotting and micro‑clotting may result in thromboembolic events and multi‑organ failure. However, early and late TIC are not mutually exclusive, and the transition between the two may occur within minutes or hours or be delayed for days.¹,³,⁴

Historically, TXA has been supported in literature to prevent fibrinolysis and reduce surgical blood loss in major surgeries including cardiac, orthopedic, liver, and vascular surgery. Trials in these settings showed that TXA reduced the need for blood transfusion and that mortality was relatively rare in elective cases, without evidence of increased thromboembolic risk.

After reviewing literature supporting TXA use in surgical patients, researchers were motivated to conduct the CRASH‑2 trial, which examined TXA in trauma patients.¹

Data from the CRASH‑2 and CRASH‑3 trials have guided indications, administration timing, and cost‑effectiveness of TXA. CRASH‑2 aimed to investigate the effects of early TXA administration on death, vascular occlusive events, and transfusion requirements in trauma patients.

The trial found that all‑cause mortality and death due to bleeding were both decreased with TXA, with no increase in vascular occlusive events such as myocardial infarction, stroke, pulmonary embolism, or deep vein thrombosis.

The benefit of TXA was greatest when given early, especially within 3 hours of injury, although transfusion requirements and surgical intervention rates were similar between groups.⁵

The Military Application of Tranexamic Acid in Trauma Emergency Resuscitation Study (MATTERS) also showed a survival benefit of a 1-gram bolus of TXA, especially in patients with severe injuries, penetrating trauma, or those requiring massive transfusion protocol.⁶

While TXA use is common in the trauma bay and is often administered by EMS in the field to trauma patients at risk of hemorrhage, there are some unique uses of TXA that may also benefit the trauma patient.

CRASH‑3 evaluated the effects of TXA in traumatic brain injury (TBI), as intracranial bleeding is common after TBI and can lead to rising intracranial pressure, brain herniation, and preventable early death.

The primary outcome was head injury‑related death in hospital within 28 days of injury in patients treated with TXA within 3 hours, with the time limitation derived from CRASH‑2.

CRASH‑3 found that early TXA modestly reduced head injury‑related death in patients with mild to moderate TBI (GCS 9–15), with no increase in thrombotic complications, but showed no clear benefit in severe TBI (GCS 3–8).⁷

Together, CRASH‑2 and CRASH‑3 demonstrated that TXA can safely reduce preventable deaths from traumatic bleeding, including systemic hemorrhage and intracranial bleeding, when administered within 3 hours of injury.

Recently, the alternative methods of TXA administration before and within the trauma bay have been studied. The traditional dosing of TXA is 1-gram bolus over 10 minutes, followed by a 1-gram continuous infusion over 8 hours. Because of this dosing strategy, trauma patients occasionally do not receive the second dose of TXA.

There have been recent trials examining pre-hospital TXA administration, which has been associated with reduced mortality compared to inhospital administration especially in patients with TBI.⁸,⁹

Additionally, recent studies have examined the administration of 2-gram boluses of TXA instead of the traditional dosing strategy, with at least one trial showing clinical outcomes and 24-hour fibrinolysis state equivalence across these dosing strategies.¹⁰

Further study will be needed in this area to determine the efficacy and utility of these strategies, though pre-hospital administration of TXA has gained wider acceptance to ensure administration of TXA within the 3-hour window established by the CRASH trials. ¹¹

Topical TXA has shown promise in reducing localized bleeding, including improved control of epistaxis compared with anterior nasal packing in patients on antiplatelet therapy, and broader evidence suggests topical application can decrease bleeding across various minor procedures.¹²,¹³

Nebulized TXA has also been explored as a noninvasive option for hemoptysis, with a small trial demonstrating reduced bleeding and faster symptom resolution compared with placebo.¹⁴

Together, these alternative approaches highlight potential adjunctive uses of TXA in trauma care, though larger studies are needed to define their role.

Questions remain about TXA usage in trauma including concerns about pro‑thrombotic risk, uncertainty about patient population, debate about administration timing, and variability in prehospital versus in‑hospital protocols.²

Additionally, the risk of TXA-associated seizures has not been addressed thoroughly in the trauma population.¹

So while the use of TXA is prevalent within the trauma population, some future studies should be completed to fully elucidate TXA’s potential and risks in the trauma population.

References:

Hanley C, Callum J, Jerath A. Tranexamic Acid and Trauma Coagulopathy: Where Are We Now? Br J Anaesth. 2020:126(1). doi.org/10.1016/j.bja.2020.09.014.
Zhang G, Liu J, Zhang W, et al. Current Research Progress of Tranexamic Acid in the Management of Patients with Traumatic Injuries in Emergency Settings. Front Dis Emerg Med. 2025:3(11). doi.org/10.3389/femer.2025.1604622.
James A, Cole E, Dunser M, et al. Acute Traumatic Coagulopathy: What You Should Know, What Is Debated and What Should Come Next. Anaesth Crit Care Pain Med. 2025:44(4): 101543. doi.org/10.1016/j.accpm.2025.101543.
Moore EE, Moore HB, Kornblith LZ, et al. Trauma-Induced Coagulopathy. Nat Rev Dis Prim. 2021:7(1):1-23. doi.org/10.1038/s41572-021-00264-3.
CRASH-2 trial collaborators; Shakur H; Roberts I, et al. Effects of tranexamic acid on death, vascular occlusive events, and blood transfusion in trauma patients with significant hemorrhage (CRASH-2): a randomised, placebo-controlled trial. Lancet. 2010;376(9734)23-32.
Morrison JJ, Dubose JJ, Rasmussen TE. Military Application of Tranexamic Acid in Trauma Emergency Resuscitation (MATTERs) Study. Arch Surg. 2012:147(2):113-119. doi.org/10.1001/archsurg.2011.287.
CRASH-3 trial collaborators. Effects of tranexamic acid on death, disability, vascular occlusive events and other morbidities in patients with acute traumatic brain injury (CRASH-3): a randomised, placebo-controlled trial. Lancet. 2019; 394(10210):1713-1723.
Fouche PF, Stein C, Nichols M, et al. Tranexamic Acid for Traumatic Injury in the Emergency Setting: A Systematic Review and Bias-Adjusted Meta-Analysis of Randomized Controlled Trials. Ann Emerg Med. 2023:83(5). doi.org/10.1016/j.annemergmed.2023.10.004.
Javeed SS, Altawili MA, Almubarak LN, et al. The Effectiveness of Prehospital Administration of Tranexamic Acid in reducing Mortality in Trauma Patients: An Overview. Cureus. 2023:15(12):e49784. doi.org/10.7759/cureus.49784.
Gunn F, Stevenson R, Almuwallad A, et al. A Comparative Analysis of Tranexamic Acid Dosing Strategies in Traumatic Major Hemorrhage. J Trauma Acute Care Surg. 2024:96(2):216-224. doi.org/10.1097/TA.0000000000004177.
Fischer PE, Bulger EM, Perina DG, et al. Guidance Document for the Prehospital Use of Tranexamic Acid in Injured Patients. Prehosp Emerg Care. 2016:20(5):557-559. doi.org/10.3109/10903127.2016.1142628.
Ker K & Roberts I. Tranexamic Acid for Surgical Bleeding. BMJ. 2014: 349(12):g4934. doi.org/10.1136/bmj.g4934.
Zahed R, Jazayeri MHM, Naderi A, et al. Topical Tranexamic Acid Compared with Anterior Nasal Packing for Treatment of Epistaxis in Patients Taking Antiplatelet Drugs: Randomized Controlled Trial. Acad Emerg Med. 2018:25(3):261-266. doi.org/10.1111/acem.13345.
Wand O, Guber E, Guber A, et al. Inhaled Tranexamic Acid for Hemoptysis Treatment. Chest. 2018;154(6):1379-1384. doi.org/10.1016/j.chest.2018.09.026.