Uncontrolled massive bleeding with subsequent derangement of the coagulation system is a major challenge in the management of both surgical and seriously injured patients. Antifibrinolytics, such as tranexamic acid (TXA), are used for prophylaxis and treatment of bleeding caused by a local or generalized heart failure (HF) as well as other hemorrhagic conditions.
The CRASH-2 trial led by Dr. Ian Roberts was a large randomized, placebo-controlled trial that assessed the use of TXA in patients with or at risk of traumatic hemorrhage. This study was undertaken in 274 hospitals in 40 countries. A total of 20,211 adult trauma patients with, or at risk of, significant bleeding were randomly assigned within 8 h of injury to either TXA (loading dose 1 g over 10 min intravenously, followed by an infusion of 1 g over 8 h) or placebo. Roberts found that early (within three hours of injury) TXA treatment reduced the risk of death due to bleeding by about 30% and that treatment beyond three hours was less likely to be effective. Similar results were obtained in the WOMAN trial that explored the use of TXA in the setting of post-partum hemorrhage. The WOMAN study included 20,060 patients that were recruited from 193 hospitals in 21 countries. An individual patient data meta-analysis of the two trials showed that TXA significantly increased overall survival from bleeding, with no difference in regards to site of bleeding. As noted by Roberts with this analysis, treatment delay reduced the treatment benefit (p<0·0001). Immediate treatment improved survival by more than 70% (OR 1·72, 95% CI 1·42–2·10; p<0·0001).
Thereafter, the survival benefit decreased by 10% for every 15 min of treatment delay until 3 h, after which there was no benefit. TXA did not cause a significant increase in thrombotic events either given before or after 3 hours. As Roberts stated, “These results have important implications for patient care and suggests that pre-hospital TXA administration can substantially improve survival in patients with acute severe bleeding.”