Tranexamic acid, given to women who bleed heavily after giving birth, reduced the risk of death by 31% when given within three hours.
This trial included 20,060 women with postpartum haemorrhage who were randomly assigned to receive tranexamic acid or placebo. This is the first large study to indicate that it is safe and implies it should be considered as an early drug option for postpartum haemorrhage. In keeping with other recent research, there was no increase in the risk of blood clots.
Tranexamic acid is a drug that stops clots breaking down. Current guidance recommends giving drugs that cause the womb to contract first, such as oxytocin, and using tranexamic acid if bleeding continues.
Most of the data in this study came from low and middle-income countries, with much higher incidence of postpartum haemorrhage and poorer maternal health outcomes than the UK. This means that reduction in the already low rates of such deaths in the UK might be small.
Why was this study needed?
Obstetric haemorrhage (bleeding during pregnancy, labour or after giving birth) is the fourth largest cause of maternal deaths, with 13 deaths between 2012 and 2014 a rate of 0.56 per 100,000 maternities.
Postpartum haemorrhage (PPH) is a common type of major obstetric haemorrhage, occurring in 16% of deliveries. About 10% of women with major obstetric haemorrhage will need a hysterectomy after failure to limit bleeding.
Normally, the muscles of the womb contract after giving birth as the placenta separates from the womb. The blood vessels which had supplied the placenta are compressed and this helps to stop bleeding. Oxytocin is usually given after delivery of the baby to help this contraction.
Tranexamic acid reduces the breakdown of blood clots. Evidence has shown that it reduces the risk of death from bleeding in adults after traumatic injury.
The researchers wanted to find out if giving tranexamic acid to women early on in PPH improved outcomes.
What did this study do?
The World Maternal Antifibrinolytic (WOMAN) trial involved 20,060 women with postpartum haemorrhage (PPH), defined as blood loss of:
- more than 500ml after vaginal delivery
- more than 1000ml after caesarean section
- any amount that caused haemodynamic instability (inability to maintain blood pressure).
Women aged 16 years and over were randomly assigned to receive tranexamic acid 1g intravenously or matching placebo. All women received “usual” obstetric maternity care. A second dose could be given if bleeding continued or recurred.
Though 569 women from hospitals in the UK were included, the other 20 participating countries were of low- to middle-income, such as Ethiopia, Pakistan and Nigeria. “Usual care” may differ and the overall national death rates due to PPH are much lower in the UK.
What did it find?
- Tranexamic acid reduced the risk of death from bleeding by 19%. There were 155 deaths (1.5%) in the tranexamic acid group compared with 191 (1.9%) in the placebo group, (risk ratio [RR] 0.81, 95% confidence interval [CI] 0.65 to 1.00). This reduction in risk was still seen after researchers adjusted the results to take into account the underlying risk of bleeding between patients (RR 0.78, 95% CI 0.62 to 0.98).
- The benefits were greater in those given tranexamic acid earlier. If given before three hours the risk of death from bleeding was reduced by 31%: 89 deaths (1.2%) versus 127 (1.7%) in the placebo group (RR 0.69, 95% CI 0.52 to 0.91). Tranexamic acid did not reduce the risk of dying from bleeding if given more than three hours after birth, 66 deaths (2.6%) versus 63 (2.5%) (RR 1.07, 95% CI 0.76 to 1.51).
- There was no difference between the groups in adverse events due to blood clots, such as deep vein thrombosis, pulmonary embolus, stroke or heart attack.
What does current guidance say on this issue?
The Royal College of Obstetricians’ Green-top Guideline from 2016 recommends that clinicians should consider the use of intravenous tranexamic acid, in addition to oxytocin at caesarean section to reduce blood loss in women at increased risk of postpartum haemorrhage (PPH). They and NICE guidance from 2014 also recommend considering the use of tranexamic acid in the management of PPH.
The World Health Organisation 2017 guidelines recommend tranexamic acid if oxytocin or other drugs that cause the womb to contract fail to stop bleeding or if the bleeding is partly due to trauma.
What are the implications?
Some uncertainty remains as to the potential impact on mortality in the UK as most of the data came from countries with higher incidence of postpartum haemorrhage (PPH) and poorer maternal health outcomes.
No effect was found of tranexamic acid on blood transfusion and hysterectomy rates but this is probably a reflection of the design of the study and will need further research in the UK context.
Of note, tranexamic acid is not currently licensed for the treatment of PPH in the UK.
Citation and Funding
WOMAN Trial Collaborators. Effect of early tranexamic acid administration on mortality, hysterectomy, and other morbidities in women with post-partum haemorrhage (WOMAN): an international, randomised, double-blind, placebo-controlled trial. Lancet. 2017;389(10084):2105-16.
This project was funded by the London School of Hygiene and Tropical Medicine, an investigator initiated research grant by Pfizer Ltd, The Department of Health (grant number HICF-T2-0510-007), the Wellcome Trust (grant number WT094947) and the Bill & Melinda Gates Foundation (grant number OPP1095618).
CRASH-2 Collaborators, Shakur H, Roberts I, et al. Effects of tranexamic acid on death, vascular occlusive events, and blood transfusion in trauma patients with significant haemorrhage (CRASH-2): a randomised, placebo-controlled trial. Lancet. 2010;376(9734):23–32.
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