Highlights
- •We conducted a systematic review and meta-analysis on studies that compared standard dose with high dose IV TXA, defined as ≥2 g or ≥30 mg/kg as a single bolus, in adults (≥ 16 years of age) with hemorrhage.
- •When compared to standard dose, high dose IV TXA probably reduces transfusion requirements (OR, 0.86; 95% CI, 0.76–0.97; p = 0.01) with an uncertain effect on thromboembolic events and mortality.
- •Despite an uncertain effect on mortality, high dose TXA may be able to play an integral role in survival, particularly when the risk of exsanguination is high.
Abstract
Background
Standard dose (≤ 1 g) tranexamic acid (TXA) has established mortality benefit in trauma
patients. The role of high dose IV TXA (≥2 g or ≥30 mg/kg as a single bolus) has been
evaluated in the surgical setting, however, it has not been studied in trauma. We
reviewed the available evidence of high dose IV TXA in any setting with the goal of
informing its use in the adult trauma population.
Methods
We searched MEDLINE, EMBASE and unpublished sources from inception until July 27,
2022 for studies that compared standard dose with high dose IV TXA in adults (≥ 16
years of age) with hemorrhage. Screening and data abstraction was done independently
and in duplicate. We pooled trial data using a random effects model and considered
randomized controlled trials (RCTs) and observational cohort studies separately. We
assessed the individual study risk of bias using the Cochrane Risk of Bias for RCTs
and the Newcastle-Ottawa Scale for observational cohort studies. The overall certainty
of evidence was assessed using the GRADE approach (Grading of Recommendations Assessment,
Development and Evaluation).
Results
We included 20 studies with a combined total of 12,523 patients. Based on pooled RCT
data, and as compared to standard dose TXA, high dose IV TXA probably decreases transfusion
requirements (odds ratio [OR] 0.86, 95% confidence interval [CI] 0.76 to 0.97, moderate
certainty) but with possibly no effect on blood loss (mean difference [MD] 43.31 ml
less, 95% CI 135.53 to 48.90 ml less, low certainty), and an uncertain effect on thromboembolic
events (OR 1.33, 95% CI 0.86 to 2.04, very low certainty) and mortality (OR 0.70,
95% CI 0.37 to 1.32, very low certainty).
Conclusion
When compared to standard dose, high dose IV TXA probably reduces transfusion requirements
with an uncertain effect on thromboembolic events and mortality.
Level of Evidence
Systematic review and meta-analysis, level IV.
Keywords
To read this article in full you will need to make a payment
Purchase one-time access:
Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online accessOne-time access price info
- For academic or personal research use, select 'Academic and Personal'
- For corporate R&D use, select 'Corporate R&D Professionals'
Subscribe:
Subscribe to InjuryAlready a print subscriber? Claim online access
Already an online subscriber? Sign in
Register: Create an account
Institutional Access: Sign in to ScienceDirect
References
- Mortality in Canadian trauma systems: a multicenter cohort study.Ann Surg. 2017; 265: 212-217
Office of Disease Prevention and Health Promotion. Injury and violence prevention. Accessed May 06, 2022. https://www.healthypeople.gov/2020/topics-objectives/topic/injury-and-violence-prevention/objectives#4725.
- Quantifying the healthcare costs of treating severely bleeding major trauma patients: a national study for England.Crit Care. 2015; 19 (Published 2015 Jul 6): 276
- Epidemiology of trauma deaths: a reassessment.J Trauma. 1995; 38: 185-193
- Antifibrinolytic therapy and perioperative considerations.Anesthesiology. 2018; 128: 657-670
- Efficacy and safety of antifibrinolytic agents in spinal surgery: a network meta-analysis.Chin Med J. 2019; 132 (Engl): 577-588
- The relative efficacy of antifibrinolytics in adolescent idiopathic scoliosis: a prospective randomized trial.J Bone Joint Surg Am. 2014; 96: e80
- Enzyme-controlling medicines: introduction.Semin Thromb Hemost. 1997; 23: 493-501
- The importance of early treatment with tranexamic acid in bleeding trauma patients: an exploratory analysis of the CRASH-2 randomised controlled trial.Lancet. 2011; 377 (.e11012): 1096-1101
- 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 [published correction appears in Lancet. 2019 Nov 9;394(10210):1712].Lancet. 2019; 394: 1713-1723
- Avoidable mortality from giving tranexamic acid to bleeding trauma patients: an estimation based on WHO mortality data, a systematic literature review and data from the CRASH-2 trial.BMC Emerg Med. 2012; 12 (Published 2012 Mar 1): 3https://doi.org/10.1186/1471-227X-12-3
- Why are bleeding trauma patients still dying?.Intensive Care Med. 2019; 45: 709-711
- The independent association of massive blood loss with mortality in cardiac surgery.Transfusion. 2004; 44 (Paris): 1453-1462
- Bleeding independently associated with mortality after noncardiac surgery (BIMS): an international prospective cohort study establishing diagnostic criteria and prognostic importance.Br J Anaesth. 2021; 126: 163-171
- Chapter 10: analysing and presenting results.in: Deeks JJ Bossuyt PM Gatsonis C Cochrane handbook for systematic reviews of diagnostic test accuracy version 1.0. The Cochrane Collaboration, 2010 (Available from:)
Statistics Canada. Table 1 mean height, weight, body mass index (BMI) and prevalence of obesity, by collection method and sex, household population aged 18 to 79, Canada, 2008, 2007 to 2009, and 2005. Published Aug 17, 2011. https://www150.statcan.gc.ca/n1/pub/82-003-x/2011003/article/11533/tbl/tbl1-eng.htm.
- Chapter 8: assessing risk of bias in a randomized trial.in: Higgins J.P.T. Thomas J. Chandler J. Cumpston M. Li T. Page M.J. Welch V.A. Cochrane handbook for systematic reviews of interventions. Cochrane, 2022 (version 6.3 (updated February 2022)Available from)
The newcastle-ottawa scale (NOS) for assessing the quality of nonrandomized studies in meta-analyses. Accessed December 20, 2020. http://www.ohri.ca/programs/clinical_epidemiology/oxford.htm.
- GRADE: an emerging consensus on rating quality of evidence and strength of recommendations.BMJ. 2008; 336: 924-926
- GRADE guidelines 26: informative statements to communicate the findings of systematic reviews of interventions.J Clin Epidemiol. 2020; 119: 126-135
- Meta-analysis in clinical trials.Control Clin Trials. 1986; 7: 177-188
- Estimating the sample mean and standard deviation from the sample size, median, range and/or interquartile range.BMC Med Res Methodol. 2014; 14 (Published 2014 Dec 19): 135
- Measuring inconsistency in meta-analyses.BMJ. 2003; 327: 557-560
- Bias in meta-analysis detected by a simple, graphical test.BMJ. 1997; 315: 629-634https://doi.org/10.1136/bmj.315.7109.629
- Prospective trial of tranexamic acid in cardiac surgery.ClinicalTrials.gov Identifier, 2016 (NCT01998438Updated February 26,Accessed October 15, 2021)
- T.ranexamic acid in primary CABG surgery: high vs low dose.Minerva Anestesiol. 2004; 70: 97-107
- Efficacy of 2 gmes of intravenous transexamic acid in the reduction of post-surgical bleeding after total hip and knee replacement. Eficacia de 2 gos intravenosos de ácido tranexámico en la reducción del sangrado postoperatorio de la artroplastia total de cadera y rodilla.Rev Esp Cir Ortop Traumatol. 2016; 60: 315-324
- Randomized, controlled trial of two tranexamic acid dosing protocols in adult spinal deformity surgery [published online ahead of print, 2022 Jun 25].Spine Deform. 2022; https://doi.org/10.1007/s43390-022-00539-z
- Comparison of two tranexamic acid dose regimens in patients undergoing cardiac valve surgery.J. Cardiothorac. Vasc. Anesth. 2014; 28: 1233-1237
- Effect of two doses of tranexamic acid on fibrinolysis evaluated by thromboelastography during cardiac surgery: a randomised, controlled study.Eur J Anaesthesiol. 2014; 31: 491-498
- The dose-response relationship of tranexamic acid.Anesthesiology. 1995; 82 (Philadelphia): 383-392
- Single tranexamic acid dose to reduce perioperative morbidity in primary total hip replacement: a randomised clinical trial.Hip Int. 2014; 24: 63-68
- Single dose intravenous tranexamic acid as effective as continuous infusion in primary total knee arthroplasty: a randomised clinical trial.Arch Orthop Trauma Surg. 2015; 135: 465-471
- The antifibrinolytic and anti-inflammatory effects of a high initial-dose tranexamic acid in total knee arthroplasty: a randomized controlled trial.Int Orthop. 2019; 44: 477-486
- Efficacy of different doses and timing of tranexamic acid in major orthopedic surgeries: a randomized trial.Braz J Anesthesiol. 2020; 70: 311-317
- Effect of high- vs low-dose tranexamic acid infusion on need for red blood cell transfusion and adverse events in patients undergoing cardiac surgery: the OPTIMAL randomized clinical trial.JAMA. 2022; 328: 336-347
- Comparison of two doses of tranexamic acid in adults undergoing cardiac surgery with cardiopulmonary bypass.Anesthesiology. 2014; 120: 590-600
- Efficacy of a single dose and an additional dose of tranexamic acid in reduction of blood loss in total knee arthroplasty.J Arthroplasty. 2017; 32: 2108-2112
- Clinical study of the optimal dose of intravenous tranexamic acid guided by thrombelastogram during the perioperative period of total knee arthroplasty.Int J Clin Exp Med. 2019; 12: 6989-6998
- Application of tranexamic acid for the perioperative period of patients undergoing scoliosis correction surgery.Farmacia. 2020; 68: 1081-1090
- A comparison of high-dose and low-dose tranexamic acid antifibrinolytic protocols for primary coronary artery bypass surgery.Indian J Anaesth. 2016; 60: 94-101
- Dose optimisation of intravenous tranexamic acid for elective hip and knee arthroplasty: the effectiveness of a single pre-operative dose.Bone Joint Res. 2017; 6: 499-505
- The use of tranexamic acid in adult spinal deformity: is there an optimal dosing strategy?.Spine J. 2019; 19: 1690-1697
- Prospective clinical trial on dosage optimizing of tranexamic acid in non-emergency cardiac surgery procedures.Clin Hemorheol Microcirc. 2013; 55: 457-468
- Different dose regimens of intravenous tranexamic acid in adolescent spinal deformity surgery: a systematic review and meta-analysis.Biomed Res Int. 2020; 2020 (3101358)3101358
- Effect of tranexamic acid in patients with traumatic brain injury: a systematic review and meta-analysis.World Neurosurg. 2019; 123: 128-135
- Association of tranexamic acid with decreased blood loss in patients undergoing laminectomy and fusion with posterior instrumentation: a systematic review and meta-analysis.J Neurosurg Spine. 2022; 36: 686-688
- Tranexamic acid is associated with reduced mortality, hemorrhagic expansion, and vascular occlusive events in traumatic brain injury - meta-analysis of randomized controlled trials.BMC Neurol. 2020; 20 (-119): 119
- The efficacy and safety of intravenous tranexamic acid in reducing surgical blood loss in posterior lumbar interbody fusion for the adult: a systematic review and a meta-analysis.World Neurosurg. 2019; 122: 559-568
- Effect of tranexamic acid on thrombotic events and seizures in bleeding patients: a systematic review and meta-analysis.Critical Care. 2021; 25 (London, England-380): 380
- Different dose regimes and administration methods of tranexamic acid in cardiac surgery: a meta-analysis of randomized trials.BMC Anesthesiol. 2019; 19: 129
- 140 Killed in Action (KIA): an analysis of military personnel who died of their injuries before reaching a definitive medical treatment facility in Afghanistan (2004–2014).Emerg Med J EMJ. 2020; 37 (-838): 838
- Short-term outcome and differences between rural and urban trauma patients treated by mobile intensive care units in Northern Finland: a retrospective analysis.Scand J Trauma Resusc Emerg Med. 2015; 23: 91
- Rural risk: geographic disparities in trauma mortality.Surgery. 2016; 160: 1551-1559
Article info
Publication history
Published online: January 07, 2023
Accepted:
December 29,
2022
Received in revised form:
December 23,
2022
Publication stage
In Press Journal Pre-ProofIdentification
Copyright
© 2023 Elsevier Ltd. All rights reserved.
