Local delivery of tranexamic acid for hemorrhage control in trauma: a narrative review

Henry Peng^1*Christian Kastrap^2,3Catherine Tenn⁴Andrew Beckett^5,6

• ¹Toronto Research Centre (TRC), Defence Research and Development Canada (DRDC), Toronto, Canada
• ²Michael Smith Laboratories and Department of Biochemistry and Molecular Biology, University of British Columbia, Vancouver, Canada
• ³Versiti Blood Research Institute, Milwaukee, United States
• ⁴Defense Research and Development Canada Suffield Research Centre, Medicine Hat, Canada
• ⁵Royal Canadian Medical Services, Ottawa, Canada
• ⁶St Michael's Hospital, Toronto, Canada

Background: Uncontrolled hemorrhage, often accompanied by trauma-induced coagulopathy (TIC), is a leading cause of preventable death, accounting for 30–40% of trauma fatalities. Tranexamic acid (TXA), an antifibrinolytic agent, has been extensively studied and proven effective when administered systemically early in severe trauma. However, intravenous (IV) administration poses logistical challenges in prehospital and combat settings, and potential risk of thrombosis. Emerging strategies aim to enhance TXA delivery through localized systems and alternative routes. Objective: The review explores non-IV routes of delivering TXA for hemorrhage control in trauma, focusing on local, intramuscular (IM), intraosseous (IO), and oral routes, and novel delivery systems. Methods: A comprehensive synthesis of preclinical and clinical studies was conducted, focusing on the material preparation, characterization, hemostatic efficacy, pharmacokinetics (PK), and practical applicability of novel TXA delivery platforms. Results: Polymeric, inorganic, and composite materials demonstrated enhanced local hemostasis through rapid clot formation and multifunctional properties. Self-propelling systems enabled autonomous penetration into deep wounds, improving clotting time and survival in animal models. IM and IO routes achieved rapid systemic TXA levels comparable to IV as confirmed in both human and animal studies, while oral TXA showed limited utility in acute trauma. Despite promising results, clinical studies on local TXA delivery especially biomaterials-based and self-propelling delivery systems in trauma remain scarce. Conclusion: TXA demonstrates effectiveness in hemorrhage control through local delivery, either integrated with hemostatic materials or administered via IM and IO routes as practical alternatives to IV infusion in emergency settings. Future research should prioritize formulation optimization, integration of smart features for controlled release, and clinical validation to enable widespread adoption in prehospital and battlefield environments. While topical TXA has shown safety and efficacy in surgical contexts, additional clinical trials are required to confirm its role in traumatic hemorrhage and establish standardized protocols. These innovations offer practical and physiological advantages for managing bleeding, particularly in resource-limited and battlefield environments. Further research is needed to validate safety, scalability, and clinical efficacy across diverse trauma scenarios.