Prompt antifibrinolytic treatment crucial in acute severe haemorrhage
Immediate administration of the antifibrinolytic tranexamic acid increased the likelihood of survival in patients with acute severe haemorrhage, with efficacy reducing with every 15-minute delay in treatment, according to a large study.
“Severe bleeding must be treated urgently – minutes matter, and using tranexamic acid quickly has the potential to save thousands of lives,” said senior study author, Professor Ian Roberts from the London School of Hygiene & Tropical Medicine, London, UK.
“[T]ranexamic acid has the potential to prevent the hypoxia and acidosis that accompanies severe bleeding, but it must be given before tissue damage is irreversible,” stressed the researchers.
For this meta-analysis, researchers analysed individual patient-level data of 40,138 individuals (mean age 31.5 years, mean time to treatment 2.7 hours) from two trials (CRASH-2* and WOMAN**) where patients had been randomized to receive tranexamic acid (n=20,094) or placebo (n=20,044) in incidences of acute severe bleeding due to trauma or postpartum haemorrhage.
Of the 3,558 deaths that occurred, 40 percent (n=1,408) were due to bleeding, and 63 percent of these (n=884) occurred within 12 hours of bleeding onset. In the WOMAN trial, deaths due to postpartum haemorrhage peaked at 2–3 hours following bleeding onset among untreated women.
The administration of tranexamic acid increased overall survival from bleeding (odds ratio [OR], 1.20; p=0.001). Patients who received immediate treatment with tranexamic acid had significantly higher overall survival compared with those who received treatment later (OR, 1.72; p<0.0001), with, barring the first hour postadministration, a decrease in benefit with increasing treatment delay. [Lancet 2017;doi:10.1016/S0140-6736(17)32455-8]
There was an estimated 10 percent reduction in survival benefit with every 15-minute delay until 3 hours post-bleeding onset, following which there was no benefit.
There was no evidence of heterogeneity based on bleeding site.
“Trauma patients should be treated by paramedics at the scene of injury – many patients are getting [tranexamic acid] when they arrive at hospital which is often too late. For women with postpartum haemorrhage, bleeding deaths peak at 2 hours, so it is crucial that tranexamic acid is given as soon as life-threatening bleeding is diagnosed,” said Roberts.
Tranexamic acid administration did not increase the risk for fatal vascular occlusive events (OR, 0.73; p=0.1204) and there were fewer incidences of myocardial infarction in patients who received tranexamic acid (OR, 0.64; p=0.0371).
The researchers acknowledged the possibility of over- and underestimation of bleeding time due to mistiming of bleeding onset as well as the possibility that deaths due to bleeding were actually caused by other factors.