Tranexamic acid
Tranexamic acid is a synthetic derivative of lysine. Tranexamic acid inhibits plasminogen activation and plasmin activity through bonding to the lysine binding site, blocking binding to fibrin. Unlike factor VIIa and prothrombin complex, its effects occur primarily through preventing fibrinolysis rather than promoting coagulation.
Two large prospective trials, one among civilian trauma patients and one among more severely injured military trauma victims, both found significant benefit from use of tranexamic acid. The CRASH-2 trial was a prospective randomized controlled trial of 20,211 trauma patients randomized to tranexamic acid infusion or placebo. Tranexamic acid was associated with an absolute decrease in all-cause mortality (14.5% vs 16%), with an RR of 0.91 (CI, 0.85–0.97; P 5 .0035). Mortality from bleeding was also decreased (4.9% vs 5.7%), with an RR of 0.85 (CI, 0.76–0.96; P 5 .0077). No statistically significant increases in either venous or arterial thromboembolic complications were noted. However, benefit was only found if tranexamic acid was given within 3 hours of injury; administration after 3 hours was associated with increased mortality.
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The Military Application of Tranexamic Acid in Traumatic Emergency and Resuscitative Surgery (MATTERs) study examined a group of severely injured military trauma patients, of which 26% required MT. Tranexamic acid was administered within 1 hour of injury to 293 patients. Despite a higher injury severity, patients who received tranexamic acid had a significantly decreased unadjusted mortality (17.4% vs 23.9%). This benefit was even more pronounced among patients who received MT, with mortality decreased 13.7% (14.4% vs 28.1%). After multivariate logistic regression analysis, tranexamic acid was found to be an independent predictor of survival. Although an increase in venous thromboembolic complications was associated with tranexamic acid, it was not an independent predictor of thromboembolic complications in either the group as a whole or among patients who received MT.