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.

Gayet-Ageron A, Prieto-Merino D, Ker K, Shakur H, Ageron FX, Roberts I
Lancet 2018;391:125-132.
NATA Rating :
Review by : M. Levi
NATA Review

Antifibrinolytic treatment has been shown to be effective in reducing blood loss and transfusion requirements and in preventing death after cardiac surgery, major trauma or postpartum haemorrhage. Previous studies, in particular in patients with trauma, have shown that early treatment (before 3-6 hours after onset of bleeding) is more beneficial.

In this individual patient-level meta-analysis of randomised controlled trials that have enrolled more than 40,000 patients with acute severe bleeding after delivery or serious trauma, the precise timing of administration was related to the survival benefit of treatment with tranexamic acid. In this patient group, there were 3558 deaths, of which 40% were due to haemorrhage, and tranexamic acid significantly increased overall survival (odds ratio 1.2, 95% confidence interval 1.1-1.3). Immediate treatment (within 1 hour of clinical presentation) was related to increased survival by more than 70% (odds ratio 1.7, 95% confidence interval 1.4-2.1).

The authors calculated that effectiveness in preventing death decreased by 10% for every 15 minutes of treatment delay up to 3 hours, after which there was no longer any beneficial effect of starting tranexamic acid on reducing the risk of death. There was no increase in vascular thrombotic events in patients receiving antifibrinolytic treatment.

This is a highly relevant study showing that administration of antifibrinolytic treatment should be initiated as soon as possible after the clinical manifestation of major bleeding. Treatment with antifibrinolytics is relatively simple, cheap and seemingly not associated with major adverse events. This therapy should be administered with the least possible delay in patients with major haemorhage.

– Marcel Levi

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