Medical News Stories
Effect of Treatment Delay on the Effectiveness and Safety of Antifibrinolytics in Acute Severe Haemorrhage: A Meta-Analysis of Individual Patient-Level Data from 40138 Bleeding Patients
Gayet-Ageron A, Prieto-Merino D, Ker K, et al. Lancet. 2018; 391: 125-32.
Study Question: What effect does treatment delay have on the effectiveness of antifibrinolytics in acute severe bleeding?
Study Description: This meta-analysis evaluated randomized trials of patients given antifibrinolytics for acute severe bleeding. Studies completed between January 1, 1946 and April 7, 2017 were screened and included if they had greater than 1,000 patients and evaluated antifibrinolytic therapy including aprotinin, tranexamic acid (TXA), aminocaproic acid, and aminomethylbenzoic acid. The primary endpoint to evaluate treatment benefit was absence of death due to bleeding. Secondary endpoints were fatal and non-fatal vascular occlusive events.
Results: Two trials met criteria and included 40,138 patients that received TXA for acute severe bleeding secondary to trauma or post-partum hemorrhage. The majority of deaths due to bleeding (63%) occurred within 12 hours of bleeding onset. TXA significantly increased overall survival from bleeding related deaths (OR 1.2, 95% CI 1.08–1.33). Additionally, immediate treatment significantly improved survival from bleeding related death (OR 1.72, 95% CI 1.42-2.1) and delay in treatment reduced this benefit. The authors estimate a reduction in treatment benefit of 10% for every 15 minutes of treatment delay up to three hours, after which no benefit was observed. No increase in vascular occlusive events with TXA was observed.
Conclusion(s): Bleeding related deaths happen quickly after initial bleeding occurs and treatment delays reduce the benefit of antifibrinolytic therapy.
Perspective: Though the rate of death occurring almost immediately after TXA administration was unlikely to have been impacted by TXA and this analysis may be limited by the inclusion of only two trials with different patient populations, a clear relationship between time to therapy and mortality was observed. Although this study did not evaluate cause of delays, diagnosis, concern for adverse effects, and operational components likely contributed. Notably, TXA was not associated with any adverse effects. Pharmacists have an opportunity to play a key role in optimizing the operational component of TXA administration for bleeding patients.