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      Effects of tranexamic acid treatment in severely and non‐severely injured trauma patients

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          Abstract

          Background

          Urgent treatment with tranexamic acid (TXA) reduces bleeding deaths but there is disagreement about which patients should be treated. We examine the effects of TXA treatment in severely and non‐severely injured trauma patients.

          Study Design and Methods

          We did an individual patient data meta‐analysis of randomized trials with over 1000 trauma patients that assessed the effects of TXA on survival. We defined the severity of injury according to characteristics at first assessment: systolic blood pressure of less than 90 mm Hg and a heart rate greater than 120 beats per minute or Glasgow Coma Scale score of less than nine or any GCS with one or more fixed dilated pupils. The primary measure was survival on the day of the injury. We examined the effect of TXA on survival in severely and non‐severely injured patients and how these effects vary with the time from injury to treatment.

          Results

          We obtained data for 32,944 patients from two randomized trials. Tranexamic acid significantly increased survival on the day of the injury (OR = 1.22, 95% CI 1.11–1.34; p < .01). The effect of tranexamic acid on survival in non‐severely injured patients (OR = 1.25, 1.03–1.50) was similar to that in severely injured patients (OR = 1.22, 1.09–1.37) with no significant heterogeneity ( p = .87). In severely and non‐severely injured pateints, treatment within the first hour after injury was the most effective.

          Discussion

          Early tranexamic acid treatment improves survival in both severely and non‐severely injured trauma patients. Its use should not be restricted to the severely injured.

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          Most cited references18

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          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.

          Tranexamic acid can reduce bleeding in patients undergoing elective surgery. We assessed the effects of early administration of a short course of tranexamic acid on death, vascular occlusive events, and the receipt of blood transfusion in trauma patients. This randomised controlled trial was undertaken in 274 hospitals in 40 countries. 20 211 adult trauma patients with, or at risk of, significant bleeding were randomly assigned within 8 h of injury to either tranexamic acid (loading dose 1 g over 10 min then infusion of 1 g over 8 h) or matching placebo. Randomisation was balanced by centre, with an allocation sequence based on a block size of eight, generated with a computer random number generator. Both participants and study staff (site investigators and trial coordinating centre staff) were masked to treatment allocation. The primary outcome was death in hospital within 4 weeks of injury, and was described with the following categories: bleeding, vascular occlusion (myocardial infarction, stroke and pulmonary embolism), multiorgan failure, head injury, and other. All analyses were by intention to treat. This study is registered as ISRCTN86750102, Clinicaltrials.govNCT00375258, and South African Clinical Trial RegisterDOH-27-0607-1919. 10 096 patients were allocated to tranexamic acid and 10 115 to placebo, of whom 10 060 and 10 067, respectively, were analysed. All-cause mortality was significantly reduced with tranexamic acid (1463 [14.5%] tranexamic acid group vs 1613 [16.0%] placebo group; relative risk 0.91, 95% CI 0.85-0.97; p=0.0035). The risk of death due to bleeding was significantly reduced (489 [4.9%] vs 574 [5.7%]; relative risk 0.85, 95% CI 0.76-0.96; p=0.0077). Tranexamic acid safely reduced the risk of death in bleeding trauma patients in this study. On the basis of these results, tranexamic acid should be considered for use in bleeding trauma patients. UK NIHR Health Technology Assessment programme, Pfizer, BUPA Foundation, and J P Moulton Charitable Foundation. Copyright 2010 Elsevier Ltd. All rights reserved.
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            Effects of tranexamic acid on death, disability, vascular occlusive events and other morbidities in patients with acute traumatic brain injury (CRASH-3): a randomised, placebo-controlled trial

            (2019)
            Summary Background Tranexamic acid reduces surgical bleeding and decreases mortality in patients with traumatic extracranial bleeding. Intracranial bleeding is common after traumatic brain injury (TBI) and can cause brain herniation and death. We aimed to assess the effects of tranexamic acid in patients with TBI. Methods This randomised, placebo-controlled trial was done in 175 hospitals in 29 countries. Adults with TBI who were within 3 h of injury, had a Glasgow Coma Scale (GCS) score of 12 or lower or any intracranial bleeding on CT scan, and no major extracranial bleeding were eligible. The time window for eligibility was originally 8 h but in 2016 the protocol was changed to limit recruitment to patients within 3 h of injury. This change was made blind to the trial data, in response to external evidence suggesting that delayed treatment is unlikely to be effective. We randomly assigned (1:1) patients to receive tranexamic acid (loading dose 1 g over 10 min then infusion of 1 g over 8 h) or matching placebo. Patients were assigned by selecting a numbered treatment pack from a box containing eight packs that were identical apart from the pack number. Patients, caregivers, and those assessing outcomes were masked to allocation. The primary outcome was head injury-related death in hospital within 28 days of injury in patients treated within 3 h of injury. We prespecified a sensitivity analysis that excluded patients with a GCS score of 3 and those with bilateral unreactive pupils at baseline. All analyses were done by intention to treat. This trial was registered with ISRCTN (ISRCTN15088122), ClinicalTrials.gov (NCT01402882), EudraCT (2011-003669-14), and the Pan African Clinical Trial Registry (PACTR20121000441277). Results Between July 20, 2012, and Jan 31, 2019, we randomly allocated 12 737 patients with TBI to receive tranexamic acid (6406 [50·3%] or placebo [6331 [49·7%], of whom 9202 (72·2%) patients were treated within 3 h of injury. Among patients treated within 3 h of injury, the risk of head injury-related death was 18·5% in the tranexamic acid group versus 19·8% in the placebo group (855 vs 892 events; risk ratio [RR] 0·94 [95% CI 0·86–1·02]). In the prespecified sensitivity analysis that excluded patients with a GCS score of 3 or bilateral unreactive pupils at baseline, the risk of head injury-related death was 12·5% in the tranexamic acid group versus 14·0% in the placebo group (485 vs 525 events; RR 0·89 [95% CI 0·80–1·00]). The risk of head injury-related death reduced with tranexamic acid in patients with mild-to-moderate head injury (RR 0·78 [95% CI 0·64–0·95]) but not in patients with severe head injury (0·99 [95% CI 0·91–1·07]; p value for heterogeneity 0·030). Early treatment was more effective than was later treatment in patients with mild and moderate head injury (p=0·005) but time to treatment had no obvious effect in patients with severe head injury (p=0·73). The risk of vascular occlusive events was similar in the tranexamic acid and placebo groups (RR 0·98 (0·74–1·28). The risk of seizures was also similar between groups (1·09 [95% CI 0·90–1·33]). Interpretation Our results show that tranexamic acid is safe in patients with TBI and that treatment within 3 h of injury reduces head injury-related death. Patients should be treated as soon as possible after injury. Funding National Institute for Health Research Health Technology Assessment, JP Moulton Charitable Trust, Department of Health and Social Care, Department for International Development, Global Challenges Research Fund, Medical Research Council, and Wellcome Trust (Joint Global Health Trials scheme). Translations For the Arabic, Chinese, French, Hindi, Japanese, Spanish and Urdu translations of the abstract see Supplementary Material.
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              Trauma-induced coagulopathy

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                Author and article information

                Contributors
                francois-xavier.ageron@chuv.ch
                Journal
                Transfusion
                Transfusion
                10.1111/(ISSN)1537-2995
                TRF
                Transfusion
                John Wiley & Sons, Inc. (Hoboken, USA )
                0041-1132
                1537-2995
                24 June 2022
                August 2022
                : 62
                : Suppl 1 ( doiID: 10.1111/trf.v62.S1 )
                : S151-S157
                Affiliations
                [ 1 ] Emergency Department Lausanne University Hospital Lausanne Switzerland
                [ 2 ] Clinical Trials Unit London School of Hygiene and Tropical Medicine London UK
                Author notes
                [*] [* ] Correspondence

                Francois‐Xavier Ageron, Emergency Department, Lausanne University Hospital, Rue du Bugnon 46, 1011 Lausanne, Switzerland.

                Email: francois-xavier.ageron@ 123456chuv.ch

                Author information
                https://orcid.org/0000-0003-0520-3619
                Article
                TRF16954
                10.1111/trf.16954
                9539885
                35748686
                56f9fd62-b223-4582-a233-92262422fd8e
                © 2022 The Authors. Transfusion published by Wiley Periodicals LLC on behalf of AABB.

                This is an open access article under the terms of the http://creativecommons.org/licenses/by-nc/4.0/ License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes.

                History
                : 23 January 2022
                : 18 January 2022
                : 23 January 2022
                Page count
                Figures: 2, Tables: 3, Pages: 7, Words: 3819
                Categories
                Original Research
                Original Research
                Custom metadata
                2.0
                August 2022
                Converter:WILEY_ML3GV2_TO_JATSPMC version:6.2.0 mode:remove_FC converted:07.10.2022

                Hematology
                blood management,hemostasis
                Hematology
                blood management, hemostasis

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