Mechanism of action of tranexamic acid in bleeding trauma patients: an exploratory analysis of data from the CRASH-2 trial

Abstract

IntroductionTo investigate the mechanism of action of tranexamic acid (TXA) in bleeding trauma patients, we examined the timing of its effect on mortality. We hypothesised that if TXA reduces mortality by decreasing blood loss, its effect should be greatest on the day of the injury when bleeding is most profuse. However, if TXA reduces mortality via an anti-inflammatory mechanism its effect should be greater over the subsequent days.MethodsExploratory analysis, including per-protocol analyses, of data from the CRASH-2 trial, a randomised placebo controlled trial of the effect of TXA on mortality in 20,211 trauma patients with, or at risk of, significant bleeding. We examined hazard ratios (HR) and 95% confidence intervals for all-cause mortality, deaths due to bleeding and non-bleeding deaths, according to the day since injury. The CRASH-2 trial is registered as ISRCTN86750102 and ClinicalTrials.gov NCT00375258.ResultsThe effect of TXA on mortality is greatest for deaths occurring on the day of the injury (HR all-cause mortality = 0.83, 0.73 to 0.93). This survival benefit is only evident in patients in whom treatment is initiated within 3 hours of their injury (HR ≤3 hours = 0.78, 0.68 to 0.90; HR >3 hours = 1.02, 0.76 to 1.36). Initiation of TXA treatment within 3 hours of injury reduced the hazard of death due to bleeding on the day of the injury by 28% (HR = 0.72, 0.60 to 0.86). TXA treatment initiated beyond 3 hours of injury appeared to increase the hazard of death due to bleeding, although the estimates were imprecise.ConclusionsEarly administration of tranexamic acid appears to reduce mortality primarily by preventing exsanguination on the day of the injury.Electronic supplementary materialThe online version of this article (doi:10.1186/s13054-014-0685-8) contains supplementary material, which is available to authorized users.

Effectiveness of early administration of tranexamic acid in patients with severe trauma

“…An observational study found that tranexamic acid was associated with better survival for haemodynamically unstable injured patients with a base deficit of at least 6 mEq/l, who potentially require greater amounts of transfused blood. Survivor bias might explain the lack of association between blood transfusion amount and decreased mortality, because tranexamic acid administration correlated with extended survival and increased risk of blood transfusion during early trauma care. However, the present study also found that tranexamic acid was not associated with blood transfusion requirements in both the overall group and 24‐h survivors.…”

Use of Tranexamic Acid in Trauma Patients: An Analysis of Cost-Effectiveness for Use in Brazil

“…Estimates based on CRASH-2 data and epidemiological information from the World Health Organization (WHO) come to point out the possibility of avoiding 128,000 of the 400,000 annual deaths that occur in bleeding trauma patients around the world 22 . Study evaluating the cost-effectiveness of the use of TXA in trauma, in three different scenarios, was conducted: England (high gross domestic product, GDP, per capita), India (middle GDP per capita) and Tanzania (low GDP per capita) 6 .…”

The effectiveness and safety of tranexamic acid in bilateral total knee arthroplasty

“…[24–26] TXA can reduce blood loss by inhibiting fibrinolysis via combining with the lysine-binding sites of plasminogen. [27] Methods for application of TXA include topical, intravenous, and combined topical with intravenous. [28–30] These methods are efficient in reducing blood loss and the need for transfusion.…”