Mechanism of Action of Tranexamic Acid in Bleeding Trauma Patients

## Ian Roberts, David Prieto-Merino and Daniela Manno

Critical Care 2014, 18:685

#### Description with Key Points:

To investigate the mechanism of action of tranexamic acid (TXA) in bleeding trauma patients, the authors examined the timing of its effect on mortality. The working hypothesis was the following-- if TXA reduces mortality by decreasing blood loss, its effect should be greatest on the day of the injury when bleeding is most profuse. However, if TXA reduces mortality via an anti-inflammatory mechanism its effect should be greater over the subsequent days. This paper is an exploratory analysis, including per-protocol analyses, of data from the CRASH-2 trial, a randomized placebo controlled trial of the effect of TXA on mortality in 20,211 trauma patients with, or at risk of, significant bleeding.

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The effect of TXA on mortality is greatest for deaths occurring on the day of the injury. This survival benefit is only evident in patients in whom treatment is initiated within 3 hours of their injury. Initiation of TXA treatment within 3 hours of injury reduced the hazard of death due to bleeding on the day of the injury by 28%. TXA treatment initiated beyond 3 hours of injury appeared to increase the hazard of death due to bleeding, although the estimates were imprecise. Early administration of tranexamic acid appears to reduce mortality primarily by preventing exsanguination on the day of the injury.

Mechanism of action of tranexamic acid in bleeding trauma patients: an exploratory analysis of data from the CRASH-2 trial
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# Take Home Message:

TXA improves survival by reducing bleeding
The effect of TXA on mortality is greatest on the day of the injury, when early TXA treatment reduces the risk of death from all causes by about 20% and death due to bleeding by about 30%.
There is a short time-window during which TXA administration can prevent exsanguination; urgent treatment may therefore be essential.
Treatment with TXA should be initiated within 3 hours of the injury to optimally reduce the chances of death due to bleeding.
TXA treatment initiated beyond 3 hours of injury appeared to increase the hazard of death due to bleeding.