Introduction

Trauma is the leading cause of death in individuals up to 45 years old and the fourth leading cause of death overall for all ages. Uncontrolled hemorrhage remains the leading cause of early mortality in major trauma, occurring as an effect of uncontrolled bleeding and trauma-induced coagulopathy.

Key Points on TXA in Trauma

  • Trauma is the leading cause of death in individuals up to 45 years old and fourth overall1
  • Uncontrolled hemorrhage is the leading cause of early mortality in major trauma2
  • TXA is an antifibrinolytic that forms a reversible complex displacing plasminogen from fibrin, inhibiting fibrinolysis4
  • TXA is readily available, simple to administer, relatively inexpensive, with minimal side effects

Pharmacology of Tranexamic Acid

Parameter Details
Dose

Loading: 1 g over 10 minutes started within 3 hours of injury

Alternative: 2 g via slow IV Push*

Maintenance: 1 g over the next 8 hours as continuous infusion

*Emerging data from prehospital and military use
Administration

Loading Dose

Administer undiluted; Max rate: 100 mg/minute

Continuous Infusion

Dilute with compatible solutions; rate not to exceed 100 mg/min
PK/PD
Vd: 9–12 L (IV) Protein binding: ~3% Half-life: ~2 hours Excretion: >95% urine unchanged
Adverse Effects
Hypersensitivity reactions Seizures & myoclonus Thromboembolic effects Ocular effects Abdominal pain Headache Back pain

Clinical Pearl

TXA must be administered within 3 hours of injury for optimal benefit. Primarily bound to plasminogen (~3%), it has a short half-life of ~2 hours and is renally eliminated largely unchanged (>95%), making it predictable in most trauma patients.

Overview of Key Evidence

Author / Year Design (n) Intervention Key Findings
Morrison, 20126 Observational
n=896 		TXA 1 g bolus + repeat PRN vs placebo
Mortality significantly reduced

All-cause mortality within 48 hrs and in-hospital mortality reduced with TXA
Roberts, 20137 RCT
n=20,211 		TXA 1 g bolus + 1 g over 8 hrs vs placebo
28-day mortality reduced

Treatment within 1 hr and 1–3 hrs significantly reduced risk of death due to bleeding
Sprigg, 20188 RCT
n=2,325 		TXA 1 g bolus + 1 g over 8 hr infusion vs placebo
Mixed results

Reduced early deaths and SAEs, but not long-term functional status
Roberts, 20199 RCT
n=12,737 		TXA 1 g bolus + 1 g over 8 hrs vs placebo
Head injury death reduced

Treatment within 3 hrs of injury reduced head injury-related death
Rowell, 2020 RCT (DB)
n=966 		TXA 1 g + 1 g 8-hr infusion vs 2 g bolus + placebo infusion vs placebo
No significant difference

No difference in 28-day mortality, neurologic function, or ICH progression
Roberts, 2020 RCT
n=12,009 		TXA 1 g + 3 g infusion vs placebo
No significant difference

No significant difference in death due to bleeding within 5 days
Bossers, 2021 Prospective Cohort
n=1,827 		Pre-hospital TXA vs no TXA in patients with TBI
Increased mortality in isolated TBI

No association with mortality at 30 days; TXA associated with increased mortality in isolated TBI
Guyette, 2021 RCT (DB)
n=927 		TXA 1 g bolus only vs 1 g + 1 g infusion vs 1 g + 1 g + 1 g infusion vs placebo
No significant difference

Prehospital TXA did not lower 30-day mortality; no differences in 24-hr or in-hospital mortality
Mahmood, 2021 RCT
n=1,767 		TXA 1 g bolus + 1 g vs placebo
No benefit for IPH

No evidence that TXA prevents intraparenchymal hemorrhage expansion
Gruen, 2023 RCT (DB)
n=1,310 		TXA 1 g bolus prior + infusion vs matched placebo
No difference

No difference in survival with favorable functional outcome at 6 months or 6-month mortality

Clinical Conclusions

Bottom Line

TXA has been studied across pre-hospital, hospital, and combat settings. Early evidence (CRASH-2) demonstrated mortality benefit, but subsequent trials in TBI and prehospital populations have shown mixed results. TXA remains widely adopted due to its favorable safety profile, low cost, and ease of administration.

TXA has been studied in pre-hospital, hospital, and combat settings in patients who have sustained a traumatic injury.

Efficacy was demonstrated in some studies, while other studies failed to show a significant difference in outcomes.

Dosing varied significantly across studies, however one regimen has been widely adopted: 1 g bolus + 1 g over 8 hours.

TXA has minimal adverse effects, is relatively inexpensive, and readily available in many settings.

Full Reference List

  1. Rhee P, Joseph B, Pandit V, et al. Increasing trauma deaths in the United States. Ann Surg. 2014;260(1):13-21. doi:10.1097/SLA.0000000000000600
  2. Callcut RA, Kornblith LZ, Conroy AS, et al. The why and how our trauma patients die: A prospective Multicenter Western Trauma Association study. J Trauma Acute Care Surg. 2019;86(5):864-870. doi:10.1097/TA.0000000000002205
  3. Latif RK, Clifford SP, Baker JA, et al. Traumatic hemorrhage and chain of survival. Scand J Trauma Resusc Emerg Med. 2023;31(1):25. doi:10.1186/s13049-023-01088-8
  4. Hijazi N, Abu Fanne R, Abramovitch R, et al. Endogenous plasminogen activators mediate progressive intracerebral hemorrhage after traumatic brain injury in mice. Blood. 2015;125(16):2558-2567. doi:10.1182/blood-2014-08-588442
  5. Cai J, Ribkoff J, Olson S, et al. The many roles of tranexamic acid: An overview of the clinical indications for TXA in medical and surgical patients. Eur J Haematol. 2020;104(2):79-87. doi:10.1111/ejh.13348
  6. Morrison JJ, Dubose JJ, Rasmussen TE, Midwinter MJ. Military Application of Tranexamic Acid in Trauma Emergency Resuscitation (MATTERs) Study. Arch Surg. 2012;147(2):113-119. doi:10.1001/archsurg.2011.287
  7. Roberts I, Shakur H, Coats T, et al. The CRASH-2 trial: a randomised controlled trial and economic evaluation of the effects of tranexamic acid on death, vascular occlusive events and transfusion requirement in bleeding trauma patients. Health Technol Assess. 2013;17(10):1-79. doi:10.3310/hta17100
  8. Sprigg N, Flaherty K, Appleton JP, et al. Tranexamic acid for hyperacute primary IntraCerebral Haemorrhage (TICH-2): an international randomised, placebo-controlled, phase 3 superiority trial. Lancet. 2018;391(10135):2107-2115. doi:10.1016/S0140-6736(18)31033-X
  9. 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). Lancet. 2019;394(10210):1713-1723.
  10. Micromedex [Electronic version]. Greenwood Village, CO: Truven Health Analytics. Retrieved January 17, 2021, from http://www.micromedexsolutions.com/
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