Use of tranexamic acid in trauma surgical specialties: a narrative review

Thomas et al. World Journal of Emergency Surgery https://doi.org/10.1186/s13017-025-00649-9 (2025) 20:76 World Journal of Emergency Surgery Open Access REVIEW Use of tranexamic acid in trauma surgical specialties: a narrative review Hannah M. Thomas1*, Huthayfa Kahf1, Benjamin Bush2, Jeffry Nahmias3 and Philip K. Lim1 Abstract Background Tranexamic acid (TXA) is a well-known antifibrinolytic agent with increasing evidence supporting its use in trauma patients. This review evaluates the current available literature regarding TXA and its potential use to improve patient survival and reduce transfusion needs across multiple trauma surgical subspecialties and contexts. Methods A literature review was conducted on the efficacy and safety of tranexamic acid in trauma surgical specialties using PubMed (MEDLINE) and Google Scholar from database inception to October 2024. Selected articles were written in the English language and encompassed reviews, experimental studies, and basic science articles. Results There is conflicting evidence on the mortality benefit of TXA, particularly in the prehospital setting. However, multiple large, high-quality studies have shown that TXA is an effective agent to reduce bleeding after trauma. Extensive evidence exists that TXA is a safe medication, with numerous studies demonstrating no increased risk of thromboembolic events after administration of TXA in trauma settings. Additionally, multiple cost-effectiveness studies conducted in several countries have found TXA to be a highly cost-effective intervention following trauma. Conclusion TXA is a safe, effective, and cost-effective medication to reduce bleeding after trauma. Future research on TXA is needed to elucidate the potential benefit of TXA after traumatic brain and spine injury and the optimal dose and route of administration of TXA. Keywords Hemostasis, Coagulopathy, Tranexamic acid, Fibrinolysis, Trauma, Prehospital care, Massive transfusion, Hemorrhage, Resuscitation, Mortality *Correspondence: Hannah M. Thomas 1 Department of Orthopaedic Surgery, University of California, Irvine, 101 The City Drive South, Pavilion 3, Building 29A, Orange, CA 92868, USA 2 Dodge Family College of Arts and Sciences, University of Oklahoma, 660 Parrington Oval, Norman, OK 73019, USA 3 Department of Surgery, University of California, Irvine, 101 The City Drive South, Orange, CA 92868, USA Background Acute trauma is a leading cause of death in adults worldwide, with trauma-associated hemorrhage being a major contributor to morbidity and mortality in these patients [1, 2]. In addition, the concurrent development of coagulopathy secondary to trauma can further exacerbate hemorrhage due to hyperfibrinolysis, with some studies showing a mortality rate as high as 70–100% in traumatized patients in a hyperfibrinolytic state [3, 4]. Given these factors, there is increasing interest in modalities to reduce hemorrhage in trauma patients to decrease morbidity and improve patient survival. In 2010, the landmark Clinical Randomization of an Antifibrinolytic in Significant Hemorrhage (CRASH)-2 © The Author(s) 2025. Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. Thomas et al. World Journal of Emergency Surgery (2025) 20:76 trial demonstrated that empiric administration of tranexamic acid (TXA), an antifibrinolytic, resulted in a 1.5% absolute reduction in 28-day mortality among 20,211 patients with or at risk of significant bleeding [5]. Since then, numerous subsequent studies have similarly found that TXA is associated with decreased mortality and risk of bleeding after trauma. However, several more recent studies have found no significant reduction in mortality rates after TXA administration in the pre-hospital setting or in trauma patients with hyperfibrinolysis [6–8]. Given these conflicting findings, this review seeks to summarize the existing body of evidence regarding the efficacy, safety, and cost of TXA across multiple trauma contexts including in-hospital administration, pre-hospital administration, orthopaedic/spine trauma, and neurological trauma. Methods This is a narrative, non-systematic review of the efficacy and safety of tranexamic acid in trauma surgical specialties. Relevant scientific articles were identified by searching the PubMed (MEDLINE) and Google Scholar databases. Articles written from database inception to October 2024 were eligible for inclusion. Relevant ongoing clinical trials were identified and analyzed from ClinicalTrials.gov. Keywords searched were trauma, tranexamic acid, TXA, and antifibrinolytic. To identify literature related to orthopaedic and neurological trauma, additional searches were conducted adding the terms fracture, orthopaedic, neurosurgery, spine, and traumatic brain injury. For each section of the review, all identified relevant articles were screened and assessed for methodological quality by two authors. In total, 106 full-text articles were reviewed and considered for inclusion. As the total number of studies written on TXA is too large to include in a single review paper, studies of the highest methodological quality were prioritized for inclusion. Meta-analyses and large randomized controlled trials were selected over cohort studies and case reports. Selected articles were written in the English language and encompassed reviews, experimental studies, and basic science articles. Each selected article was then reviewed, and results related to the efficacy and safety profile of TXA were extracted. Mechanism of action and pharmacology Functional hemostasis depends on a delicate balance between the coagulation cascade, which creates hemostatic fibrin clots, and the fibrinolytic system, which degrades them [9]. Antifibrinolytics, like TXA, work by mitigating clot breakdown [10]. TXA competitively inhibits the lysine binding site on plasminogen, which disrupts the interaction between plasminogen and fibrin, Page 2 of 10 preventing clot breakdown [10]. TXA has a half-life of approximately two hours and is excreted via urine [11, 12]. The fibrinolytic suppression effect of TXA occurs at plasma concentrations between approximately 5 and 15 mg/L and can last up t (...truncated)