WHO updates recommendation on intravenous tranexamic acid for the treatment of postpartum haemorrhage
1 November 2017: Postpartum haemorrhage (PPH) is the leading cause of maternal mortality globally. Commonly defined as a blood loss of 500 ml or more within 24 hours after birth, it affects about 5% of all women giving birth around the world. Globally, nearly one quarter of all maternal deaths are associated with PPH, and in most low-income countries it is the main cause of maternal mortality. The majority of these could be avoided by routine PPH prevention (through active management of third stage of labour), as well as prompt and effective PPH management, including the use of uterotonics and fluid replacement.
Improving care for women around the time of childbirth to prevent and treat postpartum haemorrhage is a necessary step towards achievement of the health targets of the Sustainable Development Goals. Efforts to prevent and reduce morbidity and mortality associated with postpartum haemorrhage can reduce the profound inequities in maternal health globally. To achieve this, health-care providers, health managers, policy-makers and other stakeholders need up-to-date and evidence-based recommendations to inform clinical policies and practices.
Tranexamic acid in postpartum haemorrhage treatment
Tranexamic acid, an antifibrinolytic agent, was identified as a promising drug that could be included in PPH treatment packages. The largest trial of tranexamic acid for PPH treatment to date, the World Maternal Antifibrinolytic (WOMAN) trial, was published online in April 2017.
The WOMAN Trial was a randomized, double-blind, placebo-controlled trial, that randomized women with a clinical diagnosis of PPH (regardless of mode of birth) to a regimen of intravenous (IV) tranexamic acid or identical placebo. Nearly 200 hospitals in 21 high-, middle- and low-income countries participated, recruiting over 20 000 women. The trial authors concluded that early use (within 3 hours) of IV tranexamic acid reduces maternal death due to bleeding in women with clinically-diagnosed PPH, and that early treatment appears to optimize benefit.
WHO’s updated recommendation on use of tranexamic acid for treating postpartum haemorrhage
The updating of this recommendation was guided by standardized operating procedures in accordance with the process described in the WHO handbook for guideline development. A Guideline Development Group (GDG) was convened in August 2017 to review and consider the updated analysis on tranexamic acid, as well as consider other important factors in its use, such as values and preferences of stakeholders, resource requirements, cost-effectiveness, acceptability, feasibility and equity. Today, WHO has published an updated recommendation on the use tranexamic acid for PPH treatment, which supersedes the 2012 recommendation.
WHO now strongly recommends early use of IV tranexamic acid (within 3 hours of birth) in addition to standard care for women with clinically-diagnosed PPH following vaginal birth or caesarean section. Tranexamic acid should be used in all cases of PPH, regardless of whether the bleeding is thought to be due to genital tract trauma or other causes, including uterine atony.
The recommendation emphasized a three-hour threshold (following birth), after which tranexamic acid should not be given. This was based on an individual participant data meta-analysis of the effects of timing of tranexamic acid use, which indicate that it should be given as soon as possible to optimize benefit. Delay appears to reduce benefit, with no benefit seen after 3 hours. Tranexamic acid use beyond 3 hours in women with PPH is suspected to be potentially harmful.
Implementation of the updated WHO recommendation
Administration of tranexamic acid should be considered as part of the standard PPH treatment package, in accordance with WHO guidelines. Health facilities where emergency obstetric care is provided need to have the necessary supplies, as well as the necessary training for staff attending births, so that tranexamic acid can be administered safely by intravenous infusion. All health systems, regardless of their level of resources, need to recognise that tranexamic acid is a life-saving intervention, that should be made readily available for PPH management wherever emergency obstetric care is provided.