We were very interested in the CRASH-2 trial.1 It showed not only the efficacy of tranexamic acid, but also its excellent safety in a large cohort of patients. Although the inclusion criteria for this trial were very relevant to routine clinical practice, hypotension in a trauma patient can be related to other causes (pneumothorax, spinal cord injury, etc) and not necessarily to documented bleeding.2

The CRASH-2 trial included younger patients than in other series and therefore underestimates pre-existing occlusive lesions with their corollary of platelet antiaggregant or anticoagulant treatments that predispose to bleeding.

A high frequency of coagulopathy is established on emergency-room admission and is affected by prehospital management and the magnitude of injury (reflected by the injury severity score [ISS]). ISS is not presented in the results of the CRASH-2 trial. Organisation of the health-care system therefore has a major role.3 The CRASH-2 trial does not take into account prehospital organisation, raising the question of whether these results can be extrapolated to all health-care systems.

Since randomisation did not take into account patients in whom tranexamic acid would have been immediately indicated, this trial excluded the most critically ill patients.

Many European and North American studies on the therapeutic approach to haemorrhage have assessed the effect on mortality of the transfusion ratio of fresh frozen plasma to packed red blood cells.4 The CRASH-2 trial did not address this issue. Although this trial done on an intention-to-treat basis has a substantial statistical power, the absence of analysis of the transfusion ratio could represent a bias and a limitation to the use of tranexamic acid for the most seriously ill patients. Finally, the prevalence of thrombotic complications in the CRASH-2 trial remains relatively low compared with other studies.5

Owing to its power and rigorous methods, this trial nevertheless remains a major trial in the therapeutic approach to haemorrhage in trauma patients, showing that this inexpensive and easy-to-use molecule could be particularly useful in emergency situations without any major adverse effects.

source:Lancet