Volume 200 - Issue 5
Tranexamic acid and trauma
Author: Ian Roberts
Med J Aust 2014; 200 (5): 254-255. || doi: 10.5694/mja13.00020
Published online: 17 March 2014
Published online: 17 March 2014
Can safety evidence for tranexamic acid in elective surgery support its use in trauma?
To the Editor: Gruen and colleagues’ editorial1 contained a number of claims that are unsubstantiated.
They claimed that patients in the CRASH-2 (Clinical Randomisation of an Antifibrinolytic in Significant Haemorrhage 2) trial were not treated to “modern” standards. It is not clear what they consider “modern” and which CRASH-2 hospitals failed to provide such standards. In any case, generalisation is not a simple extrapolation from the trial to patients. To generalise, we must consider how the treatment is likely to work and what patient characteristics may be relevant to this mechanism of action. What aspects of modernity are relevant to the mechanism of action of tranexamic acid (TxA)?
Gruen et al wrote: “In 126 studies of elective surgical patients, TxA was shown to reduce the probability of blood transfusion by about one-third, albeit without significant mortality benefit.” The review cited included 129 trials in elective and emergency surgery and found fewer deaths occurred in the tranexamic acid group (risk ratio [RR], 0.61; 95% CI, 0.38–0.98; P = 0.04), although when the analysis was restricted to trials using adequate concealment there was considerable uncertainty (RR, 0.67; 95% CI, 0.33–1.34; P = 0.25).2
Gruen et al also said “the CRASH-2 study . . . is the only completed randomised controlled trial of TxA use in trauma patients”. Yet the Cochrane systematic review published in 2011 included two trials.3
Further, they said that “military and civilian trauma systems have included TxA in treatment protocols, no doubt swayed by emotive arguments that by doing so ‘more than 100 000 premature deaths could be averted’, and by promotional strategies such as the ‘Trauma Promise’”. The United Kingdom and United States military started using TxA in 2011, before estimates of the numbers of deaths averted and the trauma promise were published. The UK Surgeon General says the decision was based on the CRASH-2 trial.4 The US army also cite scientific studies.5
Gruen et al claimed that thrombotic events were reported rarely in the CRASH-2 study “probably because they were not actively sought”. Thrombotic complications were sought, and only definite thrombotic complications were recorded and reported in the CRASH-2 trial.6 However, in clinical trials, false-positive results (low specificity) bias estimates of relative effects.7
Competing interests
I was the clinical coordinator and principal investigator of the CRASH-2 trial.
References
- Gruen RL, Jacobs IG, Reade MC; PATCH-Trauma study investigators. Trauma and tranexamic acid. Med J Aust 2013; 199: 310-311. <eMJA full text>
- Ker K, Edwards P, Perel P, et al. Effect of tranexamic acid on surgical bleeding: systematic review and cumulative meta-analysis. BMJ 2012; 344: e3054. BABCIHFD
- Roberts I, Shakur H, Ker K, Coats T; CRASH-2 Trial collaborators. Antifibrinolytic drugs for acute traumatic injury. Cochrane Database Syst Rev 2011; (1): CD004896.
- British Forces News. Injured soldiers in Afghanistan saved by clotting drug [video]. 19 Jan 2011. http://www.youtube.com/watch?v=oj6P2cwwRYw (accessed Feb 2014).
- Committee on Tactical Combat Casualty Care. Tranexamic acid (TXA) in tactical combat casualty care [guideline revision recommendation]. 11 Aug 2011. http://emcrit.org/wp-content/uploads/2012/02/TXA-in-tac-combat-casualty-care.pdf (accessed Feb 2014).
- Roberts I, Shakur H, Coats T, et al. The CRASH-2 trial: a randomised controlled trial and economic evaluation of the effects of tranexamic acid on death, vascular occlusive events and transfusion requirement in bleeding trauma patients. Health Technol Assess 2013; 17: 1-79. i1142884
- Prieto-Merino D, Smeeth L, Staa TPV, Roberts I. Dangers of non-specific composite outcome measures in clinical trials. BMJ 2013; 347: f6782. i1142886