Efficacy of high dose tranexamic acid (TXA) for hemorrhage: A systematic review and meta-analysis

Mohammad Hmidan Simsam; Laurence Delorme; Dylan Grimm; Fran Priestap; Sara Bohnert; Marc Descoteaux; Rich Hilsden; Colin Laverty; John Mickler; Neil Parry; Bram Rochwerg; Christopher Sherman; Shane Smith; Jason Toole; Kelly Vogt; Sean Wilson; Ian Ball

doi:10.1016/j.injury.2022.12.029

Efficacy of high dose tranexamic acid (TXA) for hemorrhage: A systematic review and meta-analysis

Injury. 2023 Mar;54(3):857-870. doi: 10.1016/j.injury.2022.12.029. Epub 2023 Jan 8.

Authors

Mohammad Hmidan Simsam¹, Laurence Delorme², Dylan Grimm², Fran Priestap³, Sara Bohnert⁴, Marc Descoteaux⁵, Rich Hilsden⁶, Colin Laverty⁵, John Mickler⁴, Neil Parry⁷, Bram Rochwerg⁸, Christopher Sherman⁵, Shane Smith⁶, Jason Toole⁵, Kelly Vogt⁹, Sean Wilson⁵, Ian Ball¹⁰

Affiliations

¹ Schulich School of Medicine and Dentistry, Western University, 1397 Medway Park Dr, London, Ontario N6G 0Z6, Canada. Electronic address: mhmidans@uwo.ca.
² Faculty of Medicine, Queen's University, Kingston, Ontario, Canada.
³ London Health Sciences Centre Trauma Program, London, Ontario, Canada.
⁴ Defence Research and Development Canada, Canada.
⁵ Royal Canadian Medical Service, Canada.
⁶ London Health Sciences Centre Trauma Program, London, Ontario, Canada; Royal Canadian Medical Service, Canada; Department of Surgery, Western University, London, Ontario, Canada; Office of Academic Military Medicine, Western University, London, Ontario, Canada.
⁷ London Health Sciences Centre Trauma Program, London, Ontario, Canada; Department of Surgery, Western University, London, Ontario, Canada; Office of Academic Military Medicine, Western University, London, Ontario, Canada.
⁸ Department of Medicine, MacMaster University, Hamilton, Ontario, Canada; Department of Health Research Methods, Evidence and Impact, McMaster University, Hamilton, Ontario, Canada.
⁹ London Health Sciences Centre Trauma Program, London, Ontario, Canada; Department of Surgery, Western University, London, Ontario, Canada.
¹⁰ London Health Sciences Centre Trauma Program, London, Ontario, Canada; Royal Canadian Medical Service, Canada; Office of Academic Military Medicine, Western University, London, Ontario, Canada; Department of Medicine, Western University, London, Ontario, Canada; Department of Epidemiology and Biostatistics, Western University, London, Ontario, Canada.

PMID: 36746710
DOI: 10.1016/j.injury.2022.12.029

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: Hemorrhage; High dose; Mortality; Surgery; Thrombo-embolism; Tranexamic acid; Transfusion requirements; Trauma.

Publication types

Meta-Analysis
Systematic Review

MeSH terms

Adult
Antifibrinolytic Agents*
Blood Loss, Surgical / prevention & control
Blood Transfusion
Hemorrhage
Humans
Randomized Controlled Trials as Topic
Tranexamic Acid*

Substances

Tranexamic Acid
Antifibrinolytic Agents