Tranexamic acid (TXA) has been shown to decrease deaths from acute severe bleeding. To determine if time to treatment is associated with the effectiveness of TXA, these authors conducted a systematic review and only two trials met their criteria: the CRASH-2 trial of patients with severe trauma and the WOMAN trial of women with severe hemorrhage in childbirth. Each trial provided patient-level data for roughly 20,000 patients.
Among the combined total of 40,138 patients, 3558 died, including 1408 (40%) from bleeding. Most (63%) bleeding deaths occurred within 12 hours of bleeding onset. TXA significantly increased overall survival from bleeding (odds ratio, 1.20) and did not increase deaths from thrombosis (OR, 0.73). Statistical modelling suggested that the benefit from TXA decreased approximately 10% for each 15-minute delay in administration and became negligible at approximately 3 hours after bleeding onset.
The take home point is that all major trauma patients and women with severe postpartum hemorrhage should receive TXA 1 gm IV load over 10 minutes followed by an infusion of 1 gm IV over 8 hours as early as possible. The efficacy of TXA decreases with later administration and is of no benefit if given more than 3 hours after the antecedent event.
Gayet-Ageron A et al. Effect of treatment delay on the effectiveness and safety of antifibrinolytics in acute severe haemorrhage: A meta-analysis of individual patient-level data from 40 138 bleeding patients. Lancet 2017 Nov 7