Volume 200 - Issue 5
Tranexamic acid and trauma
Authors: Russell L Gruen, Ian G Jacobs and Michael C Reade
Med J Aust 2014; 200 (5): 255. || doi: 10.5694/mja13.00023
Published online: 17 March 2014
Published online: 17 March 2014
Can safety evidence for tranexamic acid in elective surgery support its use in trauma?
In reply: We agree with Jarman and Brier that there is safety evidence for tranexamic acid (TxA) in elective surgery. We hypothesise that TxA’s effects in trauma are different. At least 1.5%–2% of trauma patients develop deep vein thrombosis (DVT) and pulmonary embolism (PE), and those who do average twice as long in hospital, are twice as likely to die, and face the long-term risks of anticoagulation and vena-caval filters.1,2 TxA impairs clot breakdown, so could cause excess PEs and DVTs in this higher-risk population, as seen in the MATTERs study.
Roberts writes of “claims that are unsubstantiated”. Our uncertainty about the CRASH-2 study’s applicability to modern trauma systems is not based on hypothesised differences in mechanism of action of TxA or biological differences between populations, but rather on interactions with other treatments. Over 98% of CRASH-2 patients were recruited in developing countries.3 Blood products, prehospital and hospital-based critical care, and early interventional haemorrhage control are better supplied in wealthy developed countries than in less wealthy countries; all affect processes and outcomes of care. Investment in one Australian trauma system halved the probability of dying after severe injury4 and reduced the proportion of deaths that are potentially preventable to 1/50.5 In such systems, where most deaths are now due to unsurvivable head injury, it seems unlikely that TxA could have the same mortality benefit as in CRASH-2.
The review of TxA in surgery included 126 studies in elective surgery (not trauma) and, based on studies without high risk of bias, the findings indicate no significant mortality benefit.
Roberts’s Cochrane review of TxA in trauma included his own CRASH-2 study and a 2010 conference abstract for a never-published trial in Thailand6 stating “The full trial data will be incorporated into this systematic review once the full trial report is available”.
While the British Army might have used TxA in 2011, it wasn’t until September 2012 that their guidelines mandated TxA in their massive transfusion protocol. Roberts’s advocacy for TxA use to senior US military officers included airbrushing out one-third of the gravestones in a photograph of Arlington Cemetery, claiming that was how many of their soldiers would have survived if they had used TxA.7 Our concern is that such emotive persuasion has compromised the opportunity for reasonable, dispassionate scientific debate.
The incidence of DVT depends on approaches used for detection.8 Because ultrasound screening for trauma patients was uncommon in the CRASH-2 study, DVT was likely to be underestimated. Thus, power to detect a difference was reduced, so we disagree with Jarman and Brier that “power . . . is not an issue”. Purposely biasing comparison of adverse effects towards the null, as Roberts describes, is in our view very poor practice.
Jarman and Brier highlight the lesser mortality associated with TxA in the MATTERs study and curtly note that “death is not a condition that requires investigations”. In the MATTERs study, fewer Afghans than NATO soldiers received TxA, and mortality in Afghans after discharge from the NATO hospital was not sought. In some circumstances, death does indeed require investigation, but in MATTERs this was, unfortunately, impossible.
Competing interests
All three authors are chief investigators on the NHMRC-funded Prehospital Antifibrinolytics in Traumatic Coagulopathy and Haemorrhage (PATCH-Trauma) Study.
Acknowledgements
Russell Gruen is supported by a National Health and Medical Research Council Practitioner Fellowship.
References
- Paffrath T, Wafaisade A, Lefering R, et al; Trauma Registry of DGU. Venous thromboembolism after severe trauma: incidence, risk factors and outcome. Injury 2010; 41: 97-101.
- Knudson MM, Gomez D, Haas B, et al. Three thousand seven hundred thirty-eight posttraumatic pulmonary emboli: a new look at an old disease. Ann Surg 2011; 254: 625-632. i1142887
- United Nations Development Programme. Human Development Report 2009. Overcoming barriers: human mobility and development. New York: Palgrave Macmillan, 2009. http://hdr.undp.org/sites/default/files/reports/269/hdr_2009_en_complete.pdf (accessed Nov 2013).
- Department of Health. Victorian State Trauma Registry: 1 July 2011 to 30 June 2012 summary report. Victorian Government, 2013. http://docs.health.vic.gov.au/docs/doc/8622FC45F538C364CA257B6E00178CBE/$FILE/1303020%20VST%20report_web3.pdf (accessed Nov 2013).
- Gruen RL, Gabbe BJ, Stelfox HT, Cameron PA. Indicators of the quality of trauma care and the performance of trauma systems. Br J Surg 2012; 99 Suppl 1: 97-104. i1142893
- Yutthakasemsunt S, Kittiwattanagul W, Piyavechvirat P, et al. Tranexamic acid for preventing progressive intracranial hemorrhage in adults with traumatic brain injury: a preliminary report [abstract]. In: Abstracts. 28th Annual Meeting National Neurotrauma Symposium; 2010 Jun 14–17; Las Vegas, Nevada. J Neurotrauma 2010; 27: A1-A97. i1142895
- Roberts I. Do animal experiments inform patient care [video]? International Symposium on Systematic Reviews in Laboratory Animal Science. http://www.youtube.com/watch?v=S5gJRRLWLKU (accessed Nov 2013).
- Haut ER, Chang DC, Pierce CA, et al. Predictors of posttraumatic deep vein thrombosis (DVT): hospital practice versus patient factors - an analysis of the National Trauma Data Bank (NTDB). J Trauma 2009; 66: 994-999. i1142901