Literature Review: Is TXA Safe for Lesser Injuries?

Roberts I, Perel P, Prieto, et al. Effect of tranexamic acid on mortality in patients with traumatic bleeding: prespecified analysis of data from randomised controlled trial. BMJ, 2012 Sep 11; 345: e5,839.

Abstract

The authors examined whether the effect of tranexamic acid on the risk of death and thrombotic events in patients with traumatic bleeding varies according to baseline risk of death, and assessed the extent to which current protocols for treatment with tranexamic acid maximize benefits to patients. Design—Prespecified stratified analysis of data from the CRASH-2 trial with an estimation of the proportion of premature deaths that could potentially be averted through the administration of tranexamic acid. Participants—13,273 trauma patients in the CRASH-2 trial who were treated with tranexamic acid or placebo within three hours of injury and trauma patients enrolled in U.K. Trauma and Audit Research Network, stratified by risk of death at baseline (<6%, 6%–20%, 21%–50%, >50%). Intervention—Tranexamic acid (1 g over 10 minutes followed by 1 g over 8 hours) or matching placebo. Main Outcome Measure—Odds ratios and 95% confidence intervals for death in hospital within four weeks of injury, deaths from bleeding, and fatal and non-fatal thrombotic events associated with the use of tranexamic acid according to baseline risk of death. Unless there was strong evidence against the null hypothesis of homogeneity of effects (P<0.001), the overall odds ratio was used as the most reliable guide to the odds ratios in all strata.

Results—Tranexamic acid was associated with a significant reduction in all-cause mortality and deaths from bleeding. In each stratum of baseline risk, there were fewer deaths among patients treated with tranexamic acid. There was no evidence of heterogeneity in the effect of tranexamic acid on all-cause mortality or deaths from bleeding by baseline risk of death. In those treated with tranexamic acid, there was a significant reduction in the odds of fatal and non-fatal thrombotic events and a significant reduction in arterial thrombotic events but no significant reduction in venous thrombotic events. There was no evidence of heterogeneity in the effect of tranexamic acid on the risk of thrombotic events. If the effect of tranexamic acid is assumed to be the same in all risk strata (<6%, 6%–20%, 21%–50%, >50% risk of death at baseline), the percentage of deaths that could be averted by administration of tranexamic acid within three hours of injury in each group is 17%, 36%, 30%, and 17%, respectively. Conclusions—Tranexamic acid can be administered safely to a wide spectrum of patients with traumatic bleeding and should not be restricted to the most severely injured.

Comment

Coagulation involves the formation of a fibrin clot—platelets and other blood components held together by a fibrin mesh. Fibrinolysis is the process of plasmin cleaving the fibrin strands. Primary fibrinolysis is the continuous process by which blood clots are broken down, keeping small naturally occurring clots from enlarging and occluding blood vessels. However, fibrinolysis also dissolves clots that stop bleeding, and therefore can increase hemorrhage in cases of trauma, surgery, childbirth and other potentially life-threatening clinical events.

Tranexamic acid (TXA) inhibits the formation and action of plasmin, and was first reported to reduce fibrinolysis in 1962. It has been used to reduce menstrual and surgical bleeding for years. More recently there have been two trials that show that TXA reduces bleeding and mortality in trauma. The CRASH-2 trial involved 20,211 patients treated in 274 hospitals in 40 countries. In patients given TXA within 3 hours of injury, all-cause mortality was reduced, and mortality from blood loss decreased by nearly 30%. As important, there was no increase in death or complications from blood clots. The MATTERS trial, involving 900 combat injuries, also found that all-cause and bleeding deaths were significantly reduced.

One remaining question was whether TXA would still be effective if given to less-injured patients. In the prehospital setting it is often difficult to tell how serious (or unserious) an injury is—especially in the elderly. This study reevaluated the CRASH-2 data for patients treated in England and Wales. The authors looked at all categories of severity of injury—from less severe to critical—and found that TXA reduced mortality in all groups. Patients given TXA had less bleeding and, interestingly, also had a reduced incidence of arterial thrombosis (myocardial infarction, stroke).

Tranexamic acid is safe, inexpensive, simple to administer (1 g IV over 10 minutes), appears to be effective in reducing mortality in trauma patients of all types, and must be given within 3 hours of injury. All of that should make EMS systems, especially those with longer transport times, consider including it in their treatment protocols.

Angelo Salvucci, Jr., MD, FACEP, is medical director for the Santa Barbara County and Ventura County (CA) EMS agencies and a member of the EMS World editorial advisory board.