What information is available on the use and dosing of tranexamic acid (TXA) for major trauma?

Introduction
Hemorrhage due to traumatic injury has been a leading cause of death in the United States (US) in individuals between 1 and 46 years of age.1 Based on data from 2015, outside of military conflict, severe bleeding accounts for nearly 40% of deaths within the first 24 hours of injury. Tranexamic acid (TXA) is an antifibrinolytic agent, with its IV formulation approved by the US Food and Drug Administration (FDA) for short-term use (2 to 8 days) in patients with hemophilia to reduce or prevent hemorrhage and reduce the need for replacement therapy during and following tooth extraction.2,3 Injectable TXA also has many off-label uses, such as for the prevention of blood loss in elective cesarean sections, total knee arthroplasty, cardiac and other surgeries, and treatment for patients with intracranial hemorrhage and postpartum hemorrhage.4 Another off-label use of TXA is treatment of bleeding in trauma patients.

In 2010, results from the clinical randomization of an antifibrinolytic in significant hemorrhage (CRASH-2) trial, an international, randomized, placebo-controlled trial assessing the use of TXA in bleeding trauma patients, were published.5 This study enrolled adult trauma patients with significant hemorrhage (defined in the study as systolic blood pressure $\lt$90 mmHg or heart rate $\gt$110 beats per minute, or both), or patients who were considered to be at risk of significant hemorrhage; patients also had to be within 8 hours of injury. Those randomized to TXA received a loading dose of 1 gram, infused over 10 minutes, followed by an IV infusion of 1 gram over 8 hours. For the primary outcome of death in hospital within 4 weeks of injury, death from any cause was significantly reduced with TXA, occurring in 14.5% of patients treated with TXA versus 16.0% of patients treated with placebo (relative risk [RR], 0.91; 95% 0.85 to 0.97; p=0.0035). The risk of death due to bleeding was also significantly reduced, occurring in 4.9% treated with TXA versus 5.7% with placebo (RR, 0.85; 95% CI, 0.76 to 0.96; p=0.007).

The Military Application of Tranexamic Acid in Trauma Emergency Resuscitation (MATTERs) study and additional studies have also found benefit from TXA use in trauma patients.6-8 An exploratory analysis of the CRASH-2 trial found that the greatest mortality benefit occurs when TXA is given within 1 hour of injury; treatment given after 3 hours of injury appeared to increase the risk of death due to bleeding.9 Several professional organizations also discuss the use of TXA in trauma patients; some of which provide dosage recommendations.10-16 This review summarizes the use and dosages of TXA currently described in the literature for its off-label indication of major trauma in adults.

Overview of Tranexamic Acid
Tranexamic acid is a synthetic lysine analog and an antifibrinolytic agent.2-4 Its antifibrinolytic mechanism of action works through reversible, competitive inhibition by binding to the lysine-binding sites on plasmin (the activated form of plasminogen). This binding of TXA thereby prevents the binding of plasmin to fibrin monomers, preserves and stabilizes fibrin’s matrix structure, and thus reduces bleeding.

The FDA-recommended dose of TXA for its labeled indication of short-term use to reduce or prevent hemorrhage in tooth extractions in patients with hemophilia is 10 mg/kg actual body weight administered as a single IV dose immediately before tooth extractions.2,3 Tranexamic acid may also be administered via IV for 2 to 8 days following tooth extraction at a dose of 10 mg/kg actual body weight 3 to 4 times daily. Dosage adjustments are recommended for patients with moderate to severe renal impairment. The single-dose ampules and single-dose vial injection formulations of TXA have a boxed warning that the product is for IV use only, as serious, including fatal, adverse reactions, including seizures and cardiac arrhythmias, have occurred when it was inadvertently administered via the neuraxial route. Table 1 summarizes additional safety information from the prescribing information for injectable formulations of TXA.

Table 1. Summary of safety information of IV tranexamic acid2,3
FormulationsContraindicationsAdditional Warnings and PrecautionsCommon Adverse ReactionsDrug Interactions
Single-dose ampules for injection2

Single-dose vials for injection2

Single-dose bag with sodium chloride for IV use3		As a neuraxial (ie, intrathecal, epidural) injection (single-dose ampules and vials for injection only)

In patients with subarachnoid hemorrhage, due to the risk of cerebral edema and cerebral infarction

In patients with active intravascular clotting

In patients with severe hypersensitivity to the drug or any of the product ingredients		Risk of medication errors due to the incorrect route of administration (single-dose ampules and vials for injection only)

Risk of thrombosis; risk increased with concomitant use of products that are prothrombotic (eg, factor IX complex concentrates)

May cause seizures (focal and generalized)

Hypersensitivity reactions, including anaphylactic reactions, have been reported with use

Visual disturbances have been observed with use in cats and dogs

May cause dizziness		Nausea

Vomiting

Diarrhea

Allergic dermatitis

Giddiness

Hypotension

Thromboembolic events		Prothrombotic medical products, including hormonal contraceptives; avoid concomitant use

Chlorpromazine; concomitant use may result in increased risk of bleeding (single-dose bag with sodium chloride for IV use only)
Abbreviations: IV= intravenous

Review of Key Evidence
Several professional organizations have developed recommendations regarding the use of TXA in trauma patients.10-16 Two sets of guidelines, one from the Enhanced Recovery After Surgery (ERAS) Society and International Association of Trauma Surgery and Intensive Care (IATSIC), and another from the European Society for Vascular Surgery (EVAS), provide several recommendations related to trauma care in general, and include statements on TXA.10-13 Another guideline from the Eastern Association for the Surgery of Trauma (EAST) was developed specifically for the use of TXA in the management of injured patients at risk of hemorrhage.14 The Joint Trauma System (JTS) of the US Department of Defense has a guideline on anesthesia for trauma patients that includes recommendations regarding TXA.15 In addition to these guidelines, a joint position statement on TXA in trauma was developed by The National Association of Emergency Medical Services (NAEMSP), American College of Emergency Physicians (ACEP), and the American College of Surgeons—Committee on Trauma (ACS-COT).16

The collaborative consensus guidelines for Enhanced Recovery After Trauma and Intensive Care (ERATIC), developed by ERAS and IATSIC, contain 37 recommendations for the acute trauma patient, including pre-hospital, resuscitation room, intra-operative, post-operative, and intensive care.10-12 Two recommendations in these ERATIC guidelines mention the use of TXA. One of these states that TXA may be administered as per local policies as part of a set of recommendations on pre-hospital interventions that improve survival and reduce hospital length of stay in major trauma and polytrauma patients.10 In another statement on the role of supplemental medications and procoagulant blood products in the trauma patient, the ERATIC guidelines state that TXA should be considered in different trauma systems depending on pre-hospital transfer times and access to appropriate tests and assays for monitoring.11

The ESVS developed guidelines containing 105 recommendations specifically for the care of patients with vascular trauma.13 Early administration of TXA for all severely bleeding patients with vascular trauma is recommended as part of resuscitation. The ESVS also states that the dosage should follow standard national and international guidelines based on existing trial data, including CRASH-2 (ie, 1 gram loading dose, followed by 1 gram infusion over 8 hours).

The EAST practice management guideline on the use of TXA in the management of injured patients at risk of hemorrhage, including in the pre-hospital and hospital settings, was developed through a systematic review and meta-analysis.14 Overall, EAST makes conditional recommendations in favor of TXA use in these patients in both the pre-hospital and hospital settings. While EAST poses the question as to whether a high-dose (3 to 4 grams) initial bolus of TXA is preferred versus a low-dose (1 to 2 grams) initial bolus, there was a lack of conclusive evidence to recommend for or against the use of an initial higher dose. One of the studies cited related to this statement was the TAMPITI trial, a single-center, double-blind, randomized controlled trial that compared placebo to a 2-gram or a 4-gram IV bolus of TXA in adult trauma patients with severe injury.16 For several outcomes, including intensive care unit (ICU) admission, ICU-free days, and 28-day mortality, there was no significant difference between the 2 different dosages of TXA and placebo.

Several clinical practice guidelines for battlefield medicine have been developed by JTS to support its mission: “to improve trauma readiness and outcomes through evidence-driven performance improvement.”18 One of these JTS guidelines is Anesthesia for Trauma Patients, which incorporates induction and maintenance of anesthesia into an ongoing resuscitation during surgery for a trauma patient in extremis.15 In a 2023 update, the guideline added the recommendation that a TXA 2-gram bolus is now favored over the traditional 1-gram pre-hospital bolus followed by the 1-gram infusion over 8 hours, and that the 2-gram bolus of TXA should be given as close to the time of injury as possible and not outside of the 3-hour window. Part of the rationale for this recommendation is based on results from a multicenter, double-blinded, randomized controlled trial assessing the efficacy of early TXA administration in traumatic brain injury (TBI) in the out-of-hospital setting.19 In this study, patients aged 15 years or older with moderate or severe blunt or penetrating TBI were randomized to 1 of 3 interventions to be given within 2 hours of injury: TXA 1 gram IV bolus out-of-hospital, followed by TXA, 1 gram infusion over 8 hours in-hospital; TXA 2 grams IV bolus out-of-hospital, followed by an in-hospital 8-hour placebo infusion; or an out-of-hospital placebo bolus followed by an in-hospital placebo infusion. For the primary outcome of favorable neurologic function at 6 months (Glasgow Outcome Scale-Extended score $\gt$4 [moderate disability or good recovery]), there were no significant differences between the groups. However, in a subgroup analysis in patients with confirmed intracranial hemorrhage, there was greater improvement in the Glasgow Coma Scale with the 2-gram bolus dose of TXA compared with the 1-gram bolus plus the 1-gram infusion of TXA.15,19

A summary of the key dosing recommendation statements made by professional organizations is presented in Table 2. For additional information on the statements, please refer to the full clinical practice guideline or position statement by the professional organizations or societies referenced.

Table 2. Summary of key guideline or position statements on TXA13-15
Document name and authoring organization(s)Scope/patient populationRecommendation statements related to TXA dosingEvidence rating or rationale, if provided
The Use of TXA in the Management of Injured Patients at Risk of Hemorrhage: A Systematic Review and Meta-Analysis and an EAST Practice Management Guideline (2025)14Pre-hospital environment and inpatient setting use of TXA in injured adult trauma patients at risk of hemorrhage (defined as SBP ≤90 mmHg or a heart rate ≥110 beats/minute or clinical suspicion for active hemorrhage)Cannot recommend for or against the use of high-dose initial bolus (3 to 4 grams) of TXAStatement given due to the heterogeneity and paucity of conclusive evidence of TXA dosing regimens
JTS Clinical Practice Guideline: Anesthesia for Trauma Patients (2023)15Induction and maintenance of anesthesia into an ongoing resuscitation during surgery for a military trauma patient in extremisTXA 2-gram bolus is now favored and should be given as close to the time of injury as possible, and not outside of the 3-hour windowFurther detailed analysis of timing and dosing of TXA regimens is ongoing; in the meantime, it is safe to administer an initial 2-gram bolus
TXA in Trauma: A Joint Position Statement and Resource Document of NAEMSP, ACEP, and ACS-COT (2025)16Use of IV TXA for injured patients in the EMS settingIdeal dose, rate, and route of pre-hospital administration has not been determined for adult trauma patients with hemorrhagic shock; current evidence suggests either a 1-gram IV or IO dose (followed by a hospital-based 1-gram infusion over 8 hours) or a 2-gram IV or IO dose as an infusion or slow pushEvidence related to TXA dosing pre-hospital is sparse
If used for adult trauma patients, pre-hospital TXA administration should be given to patients with clinical signs of hemorrhagic shock and no later than 3 hours post-injuryThere is no evidence to suggest improved clinical outcomes from TXA initiation beyond this time or in those without clinically significant bleeding
Abbreviations: ACEP=American College of Emergency Physicians; ACS-COT=American College of Surgeons—Committee on Trauma; EAST=Eastern Association for the Surgery of Trauma Practice Management Guideline; EMS=emergency medical services; IO=intraosseous; IV=intravenous; JTS=Joint Trauma System; NAEMSP=National Association of Emergency Medical Services; SBP=systolic blood pressure; TXA=tranexamic acid.

Discussion
A literature search to identify any new or additional evidence on the use and dosing of TXA for trauma, with a focus on meta-analysis and randomized controlled trials, was conducted. No relevant studies were found specific to adult trauma patients outside of what has already been evaluated in the guidelines and statements included in this review. The use of TXA has been recommended in adult trauma patients with hemorrhage shock, severely bleeding patients with vascular trauma, and conditionally for trauma patients at risk of hemorrhage.10-16

Dosing recommendations for TXA are not well established, potentially due to differences in the specific trauma populations and outcomes reported in clinical studies. The most common dosing regimen discussed for trauma is a 1-gram IV bolus of TXA pre-hospital as soon as possible or within 3 hours of injury, followed by a 1-gram infusion over 8 hours in-hospital.5-16,19 A 2-gram bolus of TXA as soon as possible after injury is currently recommended by JTS.15 Additional studies may help verify the optimal dosing regimen across the different sub-populations of trauma patients. Collaboration among trauma centers, emergency medical services (EMS), healthcare systems, and EMS providers, as well as consideration of the usual patient populations and resources available, is necessary when considering the pre-hospital and in-hospital use and dosing of TXA.

References

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Prepared by:
Jacqueline Wasynczuk, PharmD
Clinical Assistant Professor, Drug Information Specialist
University of Illinois at Chicago Retzky College of Pharmacy

March 2026

The information presented is current as February 20, 2026. This information is intended as an educational piece and should not be used as the sole source for clinical decision-making.