The importance of early treatment with tranexamic acid in bleeding trauma patients: an exploratory analysis of the CRASH-2 randomised controlled trial.

Roberts I, Shakur H, Afolabi A, et al.
Lancet 2011;377(9771):1096-1101.
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Review by : M. Levi
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The randomized placebo-controlled CRASH-2 study, published in 2010, showed that treatment with tranexamic acid (1 gram over 10 minutes followed by another gram over 8 hours) resulted in a reduction of mortality in trauma patients with significant hemorrhage. In this follow-up analysis focusing on death due to bleeding, in the same cohort of about 20,000 patients the authors find that timing of treatment is strongly related to the effectiveness of the intervention. In the CRASH-2 study 1063 deaths (about one third) were due to bleeding. Early treatment markedly reduced the risk of death due to bleeding in the tranexamic acid group (5.3%) compared to placebo (7.7%). When treatment was initiated between one and three hours after the injury, a similar effect was seen. However, tranexamic acid given beyond a three hours time window was not effective and, instead, resulted in a higher mortality (4.4% in the tranexamic acid group compared to 3.1% in the placebo group). Severity of bleeding, as categorized by the drop in systolic blood pressure, had no effect on the efficacy of tranexamic acid.

These results underline that the beneficial effect of tranexamic acid in trauma patients occurs in the (very) early phase after severe trauma. The accompanying editorial suggests that tranexamic acid should be administered in the pre-hospital phase, which is feasible in practice due to its low cost, easy storage, and relative safety. The harmful effect of tranexamic acid beyond three hours needs to be elucidated. Hypothetically, in this phase other factors influence the derangement of coagulation, such as hypothermia and acidosis as well as disseminated intravascular coagulation. It may well be that in such situations, inhibition of fibrinolysis, as achieved by tranexamic acid, is not desirable.

– Marcel Levi