Early administration of tranexamic acid in trauma patients

We congratulate the CRASH-2 collaborators1The CRASH-2 collaboratorsThe importance of early treatment with tranexamic acid in bleeding trauma patients: an exploratory analysis of the CRASH-2 randomised controlled trial.Lancet. 2011; 377: 1096-1101Summary Full Text Full Text PDF PubMed Scopus (760) Google Scholar on their multicentre, multicontinent initiative. However, we think that some results require further explanation. First, time between injury and administration of tranexamic acid is not precisely defined. The collaborators subdivided the time from injury to treatment (≤1 h, >1–3 h, >3 h); however, table 2 clearly shows that these times were not equally distributed between the different participating continents. Differences between organisation of out-of-hospital emergency services could largely explain this finding. The French system, for example, allows direct admission of 80% of major trauma patients to a specialised trauma centre within 3 h of the injury.2Yeguiayan JM Garrigue D Binquet C et al.Medical pre-hospital management reduces mortality in severe blunt trauma: a prospective epidemiological study.Crit Care. 2011; 15: R34Crossref PubMed Scopus (62) Google Scholar Second, patients from the CRASH-2 study seemed to be younger than in other similar studies,2Yeguiayan JM Garrigue D Binquet C et al.Medical pre-hospital management reduces mortality in severe blunt trauma: a prospective epidemiological study.Crit Care. 2011; 15: R34Crossref PubMed Scopus (62) Google Scholar, 3Stiell IG Nesbitt LP Pickett W et al.The OPALS Major Trauma Study: impact of advanced life-support on survival and morbidity.CMAJ. 2008; 178: 1141-1152Crossref PubMed Scopus (192) Google Scholar and were therefore probably less frequently treated with anticoagulants and antiplatelet agents, both of which can substantially increase bleeding after trauma and interfere with tranexamic acid effects. Also, the initial presentation of CRASH-2 patients suggests that they were less severely injured than those in other studies.2Yeguiayan JM Garrigue D Binquet C et al.Medical pre-hospital management reduces mortality in severe blunt trauma: a prospective epidemiological study.Crit Care. 2011; 15: R34Crossref PubMed Scopus (62) Google Scholar, 3Stiell IG Nesbitt LP Pickett W et al.The OPALS Major Trauma Study: impact of advanced life-support on survival and morbidity.CMAJ. 2008; 178: 1141-1152Crossref PubMed Scopus (192) Google Scholar The injury severity score (ISS) was not assessed in the CRASH-2 study. ISS classification would have identified the severity categories of patients for whom tranexamic acid would be of greatest value. This is important since the effect of tranexamic acid seems to be significant only for penetrating trauma and not blunt trauma. Third, the primary outcome chosen by the collaborators integrated fatalities from bleeding, analysed according to the time from injury to tranexamic acid administration, and to the severity of haemorrhage as assessed by systolic blood pressure. However, arterial hypotension after trauma is not always linked to haemorrhage. Moreover, transfusion requirements and strategies and the interventional haemostasis process should have been specified, again in relation to patients who would have benefited most from tranexamic acid administration. Fourth, the reason for an increase in risk of death from bleeding when tranexamic acid was given after 3 h is not considered in the discussion. The explanation of a “chance finding” proposed by the collaborators is irrelevant, since this reasoning could equally be applied to the decrease in deaths (positive result) after treatment 1 h or less after injury. We thank David Baker (Department of Anesthesiology and Critical Care, Hôpital Necker - Enfants Malades, Parism, France) for reviewing this Correspondence. We declare that we have no conflicts of interest. Early administration of tranexamic acid in trauma patients – Authors' replyWe are pleased to hear that the pre-hospital medical system in France means that tranexamic acid can be given to bleeding trauma patients very soon after injury. Given our results,1 this early treatment should improve patients' outcomes. Full-Text PDF