{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T05:22:03Z","timestamp":1790832123877,"version":"4.1.0"},"reference-count":52,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,3,14]],"date-time":"2025-03-14T00:00:00Z","timestamp":1741910400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Med."],"abstract":"<jats:sec><jats:title>Background<\/jats:title><jats:p>As an anti-fibrinolytic agent, tranexamic acid (TXA) is widely recognized for its efficacy in managing hemorrhagic conditions. Prehospital application of TXA has been reported in recent years, but its benefits in trauma patients remain debated.<\/jats:p><\/jats:sec><jats:sec><jats:title>Materials and methods<\/jats:title><jats:p>A literature search was conducted across databases including PubMed, Cochrane Library, Embase, Web of Science, SCOPUS, and the Cochrane Central Register for Clinical Trials from inception to October 2024, focusing on studies related to prehospital TXA and clinical outcomes in trauma patients. The Cochrane Risk of Bias 2 Tool was applied to assess the quality of randomized control trials (RCTs), while the Newcastle-Ottawa Scale was used for observational cohort studies. Data were pooled under a random- or fixed-effects model using RevMan 5.4 with odds ratio (OR) and 95% confidence interval (CI) as the effect measures.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>A total of 286 publications were identified from the initial database search, and 12 studies, including five RCTs and seven observational cohort studies with a total of 12,682 patients, were included. Significant early survival benefits were observed in patients receiving prehospital TXA compared to those not receiving prehospital treatment. Compared to the control group, the prehospital TXA group exhibited a significant reduction in 24-h mortality with an OR of 0.72 and a 95% CI of 0.54\u20130.94 (<jats:italic>p<\/jats:italic> = 0.02), while no statistically significant difference in the incidence of venous thromboembolism (VTE; OR: 1.14, 95% CI: 0.98\u20131.33, <jats:italic>p<\/jats:italic> = 0.09). No significant differences were observed in other outcomes, such as 28\u201330-day mortality, overall mortality, length of hospital stay, and the incidence of multiple organ failure (all <jats:italic>p<\/jats:italic> &amp;gt; 0.05).<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Prehospital TXA decreases early (24-h) mortality in trauma patients without a significant increase in the risk of VTE and other complications, and further studies are still needed to improve and optimize its management strategy.<\/jats:p><\/jats:sec><jats:sec><jats:title>Systematic review registration<\/jats:title><jats:p><jats:ext-link>https:\/\/www.crd.york.ac.uk\/PROSPERO\/<\/jats:ext-link>, Identifier: CRD 42019132189.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fmed.2025.1552271","type":"journal-article","created":{"date-parts":[[2025,3,14]],"date-time":"2025-03-14T13:49:26Z","timestamp":1741960166000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":9,"title":["Prehospital tranexamic acid decreases early mortality in trauma patients: a systematic review and meta-analysis"],"prefix":"10.3389","volume":"12","author":[{"given":"Yi","family":"Li","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mei","family":"Tian","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wen","family":"Zhong","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiatong","family":"Zou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xin","family":"Duan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haibo","family":"Si","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2025,3,14]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"1284016","DOI":"10.3389\/fmed.2023.1284016","article-title":"Prehospital tranexamic acid in trauma patients: a systematic review and meta-analysis of randomized controlled trials","volume":"10","author":"Acharya","year":"2023","journal-title":"Front Med."},{"key":"B2","doi-asserted-by":"publisher","first-page":"S3","DOI":"10.1097\/01.ta.0000199961.02677.19","article-title":"Impact of hemorrhage on trauma outcome: an overview of epidemiology, clinical presentations, and therapeutic considerations","volume":"60","author":"Kauvar","year":"2006","journal-title":"J Trauma."},{"key":"B3","doi-asserted-by":"publisher","first-page":"185","DOI":"10.1097\/00005373-199502000-00006","article-title":"Epidemiology of trauma deaths: a reassessment","volume":"38","author":"Sauaia","year":"1995","journal-title":"J Trauma."},{"key":"B4","doi-asserted-by":"publisher","first-page":"605","DOI":"10.1097\/TA.0000000000001333","article-title":"Damage control resuscitation in patients with severe traumatic hemorrhage: a practice management guideline from the eastern association for the surgery of trauma","volume":"82","author":"Cannon","year":"2017","journal-title":"J Trauma Acute Care Surg."},{"key":"B5","doi-asserted-by":"publisher","first-page":"e250","DOI":"10.1016\/S2352-3026(22)00040-0","article-title":"Resuscitation with blood products in patients with trauma-related haemorrhagic shock receiving prehospital care (RePHILL): a multicentre, open-label, randomised, controlled, phase 3 trial","volume":"9","author":"Crombie","year":"2022","journal-title":"Lancet Haematol."},{"key":"B6","doi-asserted-by":"publisher","first-page":"693","DOI":"10.1001\/jamapediatrics.2023.1291","article-title":"Association of prehospital transfusion with mortality in pediatric trauma","volume":"177","author":"Morgan","year":"2023","journal-title":"JAMA Pediatr."},{"key":"B7","doi-asserted-by":"publisher","first-page":"1131","DOI":"10.1001\/jamasurg.2021.4529","article-title":"Evaluating the cost-effectiveness of prehospital plasma transfusion in unstable trauma patients: a secondary analysis of the PAMPer trial","volume":"156","author":"Hrebinko","year":"2021","journal-title":"JAMA Surg."},{"key":"B8","doi-asserted-by":"publisher","first-page":"30","DOI":"10.1038\/s41572-021-00264-3","article-title":"Trauma-induced coagulopathy","volume":"7","author":"Moore","year":"2021","journal-title":"Nat Rev Dis Primers."},{"key":"B9","doi-asserted-by":"publisher","first-page":"33","DOI":"10.1016\/j.ajem.2022.03.027","article-title":"Tranexamic acid\u2014a narrative review for the emergency medicine clinician","volume":"56","author":"Wang","year":"2022","journal-title":"Am J Emerg Med."},{"key":"B10","doi-asserted-by":"publisher","first-page":"292.e5","DOI":"10.1016\/j.ajem.2020.10.029","article-title":"Tranexamic acid for ACE inhibitor induced angioedema","volume":"43","author":"Wang","year":"2021","journal-title":"Am J Emerg Med"},{"key":"B11","doi-asserted-by":"publisher","first-page":"1096","DOI":"10.1016\/S0140-6736(11)60278-X","article-title":"The importance of early treatment with tranexamic acid in bleeding trauma patients: an exploratory analysis of the CRASH-2 randomised controlled trial","volume":"377","author":"Roberts","year":"2011","journal-title":"Lancet."},{"key":"B12","doi-asserted-by":"publisher","first-page":"12","DOI":"10.1186\/s40560-023-00661-8","article-title":"Prehospital tranexamic acid for trauma victims","volume":"11","author":"Omori","year":"2023","journal-title":"J Intensive Care."},{"key":"B13","doi-asserted-by":"publisher","first-page":"23","DOI":"10.1016\/S0140-6736(10)60835-5","article-title":"Effects of tranexamic acid on death, vascular occlusive events, and blood transfusion in trauma patients with significant haemorrhage (CRASH-2): a randomised, placebo-controlled trial","volume":"376","author":"Shakur","year":"2010","journal-title":"Lancet."},{"key":"B14","doi-asserted-by":"publisher","first-page":"688","DOI":"10.1001\/jamasurg.2021.0251","article-title":"Prehospital tranexamic acid administration in injured patients","volume":"156","author":"Zhang","year":"2021","journal-title":"JAMA Surg."},{"key":"B15","doi-asserted-by":"publisher","first-page":"338","DOI":"10.1001\/jamaneurol.2020.4596","article-title":"Association between prehospital tranexamic acid administration and outcomes of severe traumatic brain injury","volume":"78","author":"Bossers","year":"2021","journal-title":"JAMA Neurol."},{"key":"B16","doi-asserted-by":"publisher","first-page":"e046522","DOI":"10.1136\/bmjopen-2020-046522","article-title":"Protocol for a multicentre prehospital randomised controlled trial investigating tranexamic acid in severe trauma: the PATCH-Trauma trial","volume":"11","author":"Mitra","year":"2021","journal-title":"BMJ Open."},{"key":"B17","doi-asserted-by":"publisher","first-page":"ED000142","DOI":"10.1002\/14651858.ED000142","article-title":"Updated guidance for trusted systematic reviews: a new edition of the cochrane handbook for systematic reviews of interventions cochrane database","volume":"10","author":"Cumpston","year":"2019","journal-title":"Syst Rev."},{"key":"B18","doi-asserted-by":"publisher","first-page":"n71","DOI":"10.1136\/bmj.n71","article-title":"The PRISMA 2020 statement: an updated guideline for reporting systematic reviews","volume":"372","author":"Page","year":"2021","journal-title":"BMJ."},{"key":"B19","doi-asserted-by":"publisher","first-page":"j4008","DOI":"10.1136\/bmj.j4008","article-title":"AMSTAR 2: a critical appraisal tool for systematic reviews that include randomised or non-randomised studies of healthcare interventions, or both","volume":"358","author":"Shea","year":"2017","journal-title":"BMJ."},{"key":"B20","doi-asserted-by":"publisher","first-page":"l4898","DOI":"10.1136\/bmj.l4898","article-title":"RoB 2: a revised tool for assessing risk of bias in randomised trials","volume":"366","author":"Sterne","year":"2019","journal-title":"BMJ."},{"key":"B21","doi-asserted-by":"publisher","first-page":"359","DOI":"10.2147\/CLEP.S66677","article-title":"Quality assessment of observational studies in a drug-safety systematic review, comparison of two tools: the Newcastle-Ottawa Scale and the RTI item bank","volume":"6","author":"Margulis","year":"2014","journal-title":"Clin Epidemiol."},{"key":"B22","doi-asserted-by":"publisher","first-page":"951","DOI":"10.1111\/j.1365-2753.2008.00986.x","article-title":"Interpretation of tests of heterogeneity and bias in meta-analysis","volume":"14","author":"Ioannidis","year":"2008","journal-title":"J Eval Clin Pract."},{"key":"B23","doi-asserted-by":"publisher","first-page":"11","DOI":"10.1001\/jamasurg.2020.4350","article-title":"Tranexamic acid during prehospital transport in patients at risk for hemorrhage after injury: a double-blind, placebo-controlled, randomized clinical trial","volume":"156","author":"Guyette","year":"2020","journal-title":"JAMA Surg."},{"key":"B24","doi-asserted-by":"publisher","first-page":"419","DOI":"10.1097\/SLA.0000000000005002","article-title":"Early prehospital tranexamic acid following injury is associated with a 30-day survival benefit: a secondary analysis of a randomized clinical trial","volume":"274","author":"Li","year":"2021","journal-title":"Ann Surg."},{"key":"B25","doi-asserted-by":"publisher","first-page":"961","DOI":"10.1001\/jama.2020.8958","article-title":"Effect of out-of-hospital tranexamic acid vs placebo on 6-month functional neurologic outcomes in patients with moderate or severe traumatic brain injury","volume":"324","author":"Rowell","year":"2020","journal-title":"JAMA."},{"key":"B26","doi-asserted-by":"publisher","first-page":"127","DOI":"10.1056\/NEJMoa2215457","article-title":"Prehospital tranexamic acid for severe trauma","volume":"389","author":"Gruen","year":"2023","journal-title":"N Engl J Med."},{"key":"B27","doi-asserted-by":"publisher","first-page":"572","DOI":"10.1097\/TA.0000000000004354","article-title":"The effects of prehospital TXA on mortality and neurologic outcomes in patients with traumatic intracranial hemorrhage: a subgroup analysis from the prehospital TXA for TBI trial","volume":"97","author":"Rowell","year":"2024","journal-title":"J Trauma Acute Care Surg."},{"key":"B28","doi-asserted-by":"publisher","first-page":"139","DOI":"10.1007\/s00068-023-02262-4","article-title":"Pre-hospital tranexamic acid administration in patients with a severe hemorrhage: an evaluation after the implementation of tranexamic acid administration in the Dutch pre-hospital protocol","volume":"50","author":"Gulickx","year":"2024","journal-title":"Eur J Trauma Emerg Surg."},{"key":"B29","doi-asserted-by":"publisher","first-page":"143","DOI":"10.1186\/s13054-016-1322-5","article-title":"Prehospital administration of tranexamic acid in trauma patients","volume":"20","author":"Wafaisade","year":"2016","journal-title":"Crit Care."},{"key":"B30","doi-asserted-by":"publisher","first-page":"522","DOI":"10.1213\/ANE.0000000000002708","article-title":"The impact of prehospital tranexamic acid on blood coagulation in trauma patients","volume":"126","author":"Stein","year":"2018","journal-title":"Anesth Analg."},{"key":"B31","doi-asserted-by":"publisher","first-page":"977","DOI":"10.5811\/westjem.2018.8.39336","article-title":"Tranexamic acid in civilian trauma care in the california prehospital antifibrinolytic therapy study","volume":"19","author":"Neeki","year":"2018","journal-title":"West J Emerg Med."},{"key":"B32","doi-asserted-by":"publisher","first-page":"266","DOI":"10.1016\/j.ajem.2019.04.051","article-title":"Prehospital administration of tranexamic acid in trauma patients: a 1:1 matched comparative study from a level 1 trauma center","volume":"38","author":"El-Menyar","year":"2020","journal-title":"Am J Emerg Med."},{"key":"B33","doi-asserted-by":"publisher","first-page":"277","DOI":"10.1186\/s13054-021-03701-7","article-title":"The impact of prehospital tranexamic acid on mortality and transfusion requirements: match-pair analysis from the nationwide German traumaregister DGU\u00ae","volume":"25","author":"Imach","year":"2021","journal-title":"Crit Care."},{"key":"B34","doi-asserted-by":"publisher","first-page":"179","DOI":"10.1007\/s11239-023-02898-4","article-title":"Possible effect of the early administration of tranexamic acid on myocardial injury in patients with severe trauma","volume":"57","author":"Stroda","year":"2024","journal-title":"J Thromb Thrombolysis."},{"key":"B35","doi-asserted-by":"publisher","first-page":"86","DOI":"10.1097\/TA.0000000000003767","article-title":"The effects of timing of prehospital tranexamic acid on outcomes after traumatic brain injury: subanalysis of a randomized controlled trial","volume":"94","author":"Brito","year":"2023","journal-title":"J Trauma Acute Care Surg."},{"key":"B36","doi-asserted-by":"publisher","first-page":"e075720","DOI":"10.1136\/bmj-2023-075720","article-title":"Efficacy and safety of tranexamic acid in acute haemorrhage","volume":"384","author":"Franchini","year":"2024","journal-title":"BMJ."},{"key":"B37","doi-asserted-by":"publisher","first-page":"52","DOI":"10.1097\/TA.0000000000003620","article-title":"Prehospital synergy: tranexamic acid and blood transfusion in patients at risk for hemorrhage","volume":"93","author":"Deeb","year":"2022","journal-title":"J Trauma Acute Care Surg."},{"key":"B38","doi-asserted-by":"publisher","first-page":"e135350","DOI":"10.1172\/jci.insight.135350","article-title":"Prehospital plasma is associated with distinct biomarker expression following injury","volume":"5","author":"Gruen","year":"2020","journal-title":"JCI Insight"},{"key":"B39","doi-asserted-by":"publisher","first-page":"642","DOI":"10.1097\/TA.0000000000003955","article-title":"Prehospital tranexamic acid is associated with a dose-dependent decrease in syndecan-1 after trauma: a secondary analysis of a prospective randomized trial","volume":"95","author":"Gruen","year":"2023","journal-title":"J Trauma Acute Care Surg."},{"key":"B40","doi-asserted-by":"publisher","first-page":"93","DOI":"10.1111\/anae.15866","article-title":"Major haemorrhage: past, present and future","volume":"78","author":"Shah","year":"2023","journal-title":"Anaesthesia."},{"key":"B41","doi-asserted-by":"publisher","first-page":"176","DOI":"10.1097\/ACO.0000000000001093","article-title":"Advances in hemorrhage control resuscitation","volume":"35","author":"Muldowney","year":"2022","journal-title":"Curr Opin Anaesthesiol."},{"key":"B42","doi-asserted-by":"publisher","first-page":"24","DOI":"10.1097\/TA.0000000000003121","article-title":"Outcomes after ultramassive transfusion in the modern era: an eastern association for the surgery of trauma multicenter study","volume":"91","author":"Matthay","year":"2021","journal-title":"J Trauma Acute Care Surg."},{"key":"B43","doi-asserted-by":"publisher","first-page":"927","DOI":"10.1213\/ANE.0000000000006388","article-title":"Ultramassive transfusion for trauma in the age of hemostatic resuscitation: a retrospective single-center cohort from a large US Level-1 trauma center, 2011\u20132021","volume":"136","author":"Muldowney","year":"2023","journal-title":"Anesth Analg."},{"key":"B44","doi-asserted-by":"publisher","first-page":"1859","DOI":"10.1007\/s00134-016-4608-9","article-title":"Focus on transfusion, bleeding and thrombosis","volume":"42","author":"Azoulay","year":"2016","journal-title":"Intensive Care Med."},{"key":"B45","doi-asserted-by":"publisher","first-page":"1272971","DOI":"10.3389\/fcvm.2023.1272971","article-title":"Novel strategies in antithrombotic therapy: targeting thrombosis while preserving hemostasis","volume":"10","author":"Sim","year":"2023","journal-title":"Front Cardiovasc Med."},{"key":"B46","doi-asserted-by":"publisher","first-page":"901","DOI":"10.1097\/TA.0000000000003120","article-title":"The impact of prehospital TXA on mortality among bleeding trauma patients: a systematic review and meta-analysis","volume":"90","author":"Almuwallad","year":"2021","journal-title":"J Trauma Acute Care Surg."},{"key":"B47","doi-asserted-by":"publisher","first-page":"1030","DOI":"10.3390\/jcm10051030","article-title":"Efficacy and safety of tranexamic acid in emergency trauma: a systematic review and meta-analysis","volume":"10","author":"Al-Jeabory","year":"2021","journal-title":"J Clin Med"},{"key":"B48","doi-asserted-by":"publisher","first-page":"894","DOI":"10.1213\/ANE.0000000000006356","article-title":"Factor VIII: a dynamic modulator of hemostasis and thrombosis in trauma","volume":"136","author":"Tanaka","year":"2023","journal-title":"Anesth Analg."},{"key":"B49","doi-asserted-by":"publisher","first-page":"585","DOI":"10.1097\/ALN.0000000000001760","article-title":"Acute traumatic coagulopathy: thrombin is the driver!","volume":"127","author":"Tanaka","year":"2017","journal-title":"Anesthesiology"},{"key":"B50","doi-asserted-by":"publisher","first-page":"5825","DOI":"10.3390\/ijms23105825","article-title":"Molecular mechanisms of hemostasis, thrombosis and thrombo-inflammation","volume":"23","author":"Kuijpers","year":"2022","journal-title":"Int J Mol Sci"},{"key":"B51","doi-asserted-by":"publisher","first-page":"1899","DOI":"10.1182\/blood-2017-10-784074","article-title":"The search for new antithrombotic mechanisms and therapies that may spare hemostasis","volume":"131","author":"Plow","year":"2018","journal-title":"Blood."},{"key":"B52","doi-asserted-by":"publisher","first-page":"1589","DOI":"10.1007\/s00068-021-01827-5","article-title":"The effect of prehospital tranexamic acid on outcome in polytrauma patients with associated severe brain injury","volume":"48","author":"Van Wessem","year":"2022","journal-title":"Eur J Trauma Emerg Surg."}],"container-title":["Frontiers in Medicine"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fmed.2025.1552271\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,3,14]],"date-time":"2025-03-14T13:49:30Z","timestamp":1741960170000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fmed.2025.1552271\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,3,14]]},"references-count":52,"alternative-id":["10.3389\/fmed.2025.1552271"],"URL":"https:\/\/doi.org\/10.3389\/fmed.2025.1552271","relation":{},"ISSN":["2296-858X"],"issn-type":[{"value":"2296-858X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,3,14]]},"article-number":"1552271"}}