Tranexamic Acid Use in the Surgical Arena: A Narrative Review

Objective To assess the effect of tranexamic acid on blood transfusion, thromboembolic events, and mortality in surgical patients. Design Systematic review and meta-analysis. Data sources Cochrane central register of controlled trials, Medline, and Embase, from inception to September 2011, the World Health Organization International Clinical Trials Registry Platform, and the reference lists of relevant articles. Study selection Randomised controlled trials comparing tranexamic acid with no tranexamic acid or placebo in surgical patients. Outcome measures of interest were the number of patients receiving a blood transfusion; the number of patients with a thromboembolic event (myocardial infarction, stroke, deep vein thrombosis, and pulmonary embolism); and the number of deaths. Trials were included irrespective of language or publication status. Results 129 trials, totalling 10 488 patients, carried out between 1972 and 2011 were included. Tranexamic acid reduced the probability of receiving a blood transfusion by a third (risk ratio 0.62, 95% confidence interval 0.58 to 0.65; P<0.001). This effect remained when the analysis was restricted to trials using adequate allocation concealment (0.68, 0.62 to 0.74; P<0.001). The effect of tranexamic acid on myocardial infarction (0.68, 0.43 to 1.09; P=0.11), stroke (1.14, 0.65 to 2.00; P=0.65), deep vein thrombosis (0.86, 0.53 to 1.39; P=0.54), and pulmonary embolism (0.61, 0.25 to 1.47; P=0.27) was uncertain. Fewer deaths occurred in the tranexamic acid group (0.61, 0.38 to 0.98; P=0.04), although when the analysis was restricted to trials using adequate concealment there was considerable uncertainty (0.67, 0.33 to 1.34; P=0.25). Cumulative meta-analysis showed that reliable evidence that tranexamic acid reduces the need for transfusion has been available for over 10 years. Conclusions Strong evidence that tranexamic acid reduces blood transfusion in surgery has been available for many years. Further trials on the effect of tranexamic acid on blood transfusion are unlikely to add useful new information. However, the effect of tranexamic acid on thromboembolic events and mortality remains uncertain. Surgical patients should be made aware of this evidence so that they can make an informed choice.

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.

To characterize contemporary use of tranexamic acid (TXA) in combat injury and to assess the effect of its administration on total blood product use, thromboembolic complications, and mortality. Retrospective observational study comparing TXA administration with no TXA in patients receiving at least 1 unit of packed red blood cells. A subgroup of patients receiving massive transfusion (≥10 units of packed red blood cells) was also examined. Univariate and multivariate regression analyses were used to identify parameters associated with survival. Kaplan-Meier life tables were used to report survival. A Role 3 Echelon surgical hospital in southern Afghanistan. A total of 896 consecutive admissions with combat injury, of which 293 received TXA, were identified from prospectively collected UK and US trauma registries. Mortality at 24 hours, 48 hours, and 30 days as well as the influence of TXA administration on postoperative coagulopathy and the rate of thromboembolic complications. The TXA group had lower unadjusted mortality than the no-TXA group (17.4% vs 23.9%, respectively; P = .03) despite being more severely injured (mean [SD] Injury Severity Score, 25.2 [16.6] vs 22.5 [18.5], respectively; P < .001). This benefit was greatest in the group of patients who received massive transfusion (14.4% vs 28.1%, respectively; P = .004), where TXA was also independently associated with survival (odds ratio = 7.228; 95% CI, 3.016-17.322) and less coagulopathy (P = .003). The use of TXA with blood component-based resuscitation following combat injury results in improved measures of coagulopathy and survival, a benefit that is most prominent in patients requiring massive transfusion. Treatment with TXA should be implemented into clinical practice as part of a resuscitation strategy following severe wartime injury and hemorrhage.