All Pharmacy Pearls

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.1 Uncontrolled hemorrhage is the leading cause of early mortality in major trauma.2 Trauma-associated hemorrhagic death occurs as an effect of uncontrolled bleeding and trauma-induced coagulopathy.3

Tranexamic acid is an antifibrinolytic medication that works by forming a reversible complex that displaces plasminogen from fibrin resulting in inhibition of fibrinolysis.4 Tranexamic acid is readily available, simple to administer, relatively inexpensive, with minimal side effects.

Key Points

  • Trauma is the leading cause of death in people up to 45 years old, and uncontrolled hemorrhage is the leading cause of early mortality in major trauma.
  • Tranexamic acid is an antifibrinolytic that displaces plasminogen from fibrin to inhibit fibrinolysis; it is readily available, simple to administer, and inexpensive.
  • TXA has been studied across pre-hospital, hospital, and combat settings — efficacy was demonstrated in some trials but not others.
  • Dosing varied across studies, but one regimen has been widely adopted, and TXA has minimal adverse effects.

Clinical Detail

PropertyTranexamic Acid
DoseLoading dose: 1 g over 10 minutes started within 3 hours of injury
– 2 gram via slow IV push*
Maintenance: 1 g over the next 8 hours as a continuous infusion
AdministrationLoading dose: administer undiluted
Max rate: 100 mg/minute
For continuous IV infusions: dilute with compatible solutions and administer at a rate not to exceed 100 mg/minute
PK/PDDistribution: Vd: IV: 9 to 12 L
Protein binding: ~3%, primarily to plasminogen
Half-life elimination: ~2 hours
Excretion: Urine (>95% as unchanged drug)
Adverse EffectsHypersensitivity reactions, ocular effects, seizures and myoclonus, thromboembolic effects, abdominal pain, headache, back pain

*Emerging data from prehospital and military use.

Evidence

Author, yearDesign / sample sizeIntervention & ComparisonOutcome
Morrison, 2012Observational (n = 896)TXA 1 g bolus + repeat PRN vs placeboAll-cause mortality overall, within 48 hours, and in-hospital mortality significantly reduced with TXA
Roberts, 2013Randomized placebo-controlled (n = 20,211)TXA 1 g bolus + 1 g over 8 hours vs placeboAll-cause mortality at 28 days significantly reduced by TXA; treatment within 1 hour and within 1–3 hours from injury significantly reduced the risk of death due to bleeding
Sprigg, 2018Randomized placebo-controlled (n = 2,325)TXA 1 g bolus + 1 g over 8 h infusion vs placeboPatients in the tranexamic acid group experienced a reduction in early deaths and serious adverse events, but not long-term functional status
Roberts, 2019Randomized placebo-controlled (n = 12,737)TXA 1 g bolus + 1 g over 8 hours vs placeboTreatment within 3 h of injury reduced head injury-related death
Rowell, 2020———

Note: the Rowell, 2020 entry was truncated during the original page migration; its design, intervention, and outcome could not be recovered from the source text and are not reproduced here.

Conclusions

  • Tranexamic acid has been studied in pre-hospital, hospital, and combat setting in patients who have sustained a traumatic injury
  • Efficacy of tranexamic acid was demonstrated in some studies above, while other studies failed to show a significant difference in outcomes
  • Dosing of tranexamic acid varied significantly in the above studies, however one dosing regimen has been widely adopted
  • Tranexamic acid has minimal adverse effects, is relatively inexpensive, and readily available in many settings

References

  • 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

  • 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

  • Latif RK, Clifford SP, Baker JA, et al. Traumatic hemorrhage and chain of survival. Scand J

    • Trauma Resusc Emerg Med. 2023;31(1):25. Published 2023 May 24. doi:10.1186/s13049-023-

    01088-8

  • 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

  • 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-

  • doi:10.1111/ejh.13348
  • 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

  • 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

  • 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

  • CRASH-3 trial collaborators. Effects of tranexamic acid on death, disability, vascular

    • occlusive events and other morbidities in patients with acute traumatic brain injury

  • Micromedex [Electronic version].Greenwood Village, CO: Truven Health Analytics.

    • Retrieved January 17, 2021, from http://www.micromedexsolutions.com/

Tags:tranexamic acid trauma hemorrhage CRASH-2

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