Mortality and Thrombosis in Injured Adults Receiving Tranexamic Acid in the Post-CRASH-2 Era

Abstract

Introduction The CRASH-2 trial demonstrated that tranexamic acid (TXA) reduced mortality with no increase in adverse events in severely injured adults. TXA has since been widely used in injured adults worldwide. Our objective was to estimate mortality and adverse events in adults with trauma receiving TXA in studies published after the CRASH-2 trial. Methods We systematically searched PubMed, Embase, MicroMedex, and ClinicalTrials.gov for studies that included injured adults who received TXA and reported mortality and/or adverse events. Two reviewers independently assessed study eligibility, abstracted data, and assessed the risk of bias. We conducted meta-analyses using random effects models to estimate the incidence of mortality at 28 or 30 days and in-hospital thrombotic events. Results We included 19 studies and 13 studies in the systematic review and meta-analyses, respectively. The pooled incidence of mortality at 28 or 30 days (five studies, 1538 patients) was 10.1% (95% confidence interval [CI], 7.8–12.4%) (vs 14.5% [95% CI, 13.9–15.2%] in the CRASH-2 trial), and the pooled incidence of in-hospital thrombotic events (nine studies, 1656 patients) was 5.9% (95% CI, 3.3–8.5%) (vs 2.0% [95% CI, 1.8–2.3%] in the CRASH-2 trial). Conclusion Compared to the CRASH-2 trial, adult trauma patients receiving TXA identified in our systematic review had a lower incidence of mortality at 28 or 30 days, but a higher incidence of in-hospital thrombotic events. Our findings neither support nor refute the findings of the CRASH-2 trial but suggest that incidence rates in adults with trauma in settings outside of the CRASH-2 trial may be different than those observed in the CRASH-2 trial.

Impact of a goal-directed factor-based coagulation management on thromboembolic events following major trauma

“…This haemostatic approach is a key element in the treatment of major trauma patients and recommended by the European Trauma Treatment Guidelines [1]. Frequency of thrombotic complications in trauma patients was reported in 1.1% up to 34.3% [25][26][27]. Our incidence of thromboembolic events was below 10% in both periods and thereby in the lower range.…”

Tranexamic acid: the king is dead, long live the king!

“…These facts raise concerns regarding the accuracy of detecting, diagnosing and reporting these important and relevant complications. Indeed in the view of many authors, 15,21,22 as neither the CRASH-2 nor the WOMAN trial has sufficiently assessed thromboembolism in their respective cohorts, these studies may not be the best source to provide sufficient evidence against a possible effect of TXA on increased vascular occlusive events.…”

“…In a recent systematic review and meta-analysis (nine studies, n¼1656 patients), the pooled incidence of in-hospital thrombotic events after TXA was 5.9% (95% CI, 3.3e8.5%), vs 2.0% (95% CI, 1.8e2.3%) in the CRASH-2 trial. 22 An increasing number of these side-effects are published in the trauma setting. 15 An increased risk for fibrinolytic shutdown among severely injured trauma patients receiving TXA has been described.…”

“…The results of the CRASH-2 and WOMAN trials were not reproducible in a modern, developed hospital setting in countries with high socioeconomic status. 22 TXA is not a substitute for effective surgical management of any bleeding: it does not contract an atonic uterus, nor does it tie a heavily bleeding vessel or stabilise a fractured pelvis. TXA is an effective therapy for (at least suspected) fibrinolytic bleeding.…”

“…The recently published CRASH-3 study 18 on TXA for traumatic brain injury is the first major randomised trial indicating higher RRs following application of TXA (if TXA <3 h): for thromboembolic complications (DVT: RR¼1. 22 ). Turning a blind eye to any risks of an agent instead of objective riskebenefit assessment in individual scenarios might lead to its subsequent complete removal from clinical use once risks begin to gain widespread attention.…”