To determine the effect of tranexamic acid (TXA) on postpartum bleeding in women with moderate or severe anaemia.
Postpartum haemorrhage (PPH) is responsible for about 100,000 maternal deaths every year, most of which occur in low and middle income countries. TXA reduces bleeding by inhibiting the enzymatic breakdown of fibrin blood clots. TXA decreases blood loss in surgery and reduces death due to bleeding after trauma. When given within three hours of birth, TXA reduces deaths due to bleeding in women with PPH. However, for many women, treatment of PPH is too late to prevent death. Over one-third of pregnant women in the world are anaemic and many are severely anaemic. These women have an increased risk of PPH and suffer more severe outcomes if PPH occurs. There is an urgent need to identify a safe and effective way to reduce postpartum bleeding in anaemic women.
A randomised, double-blind, placebo controlled trial.
15,000 women with moderate or severe anaemia who give birth vaginally.
The trial will be conducted in hospitals where anaemia in pregnancy is common in Africa and Asia.
The WOMAN-2 Trial is funded by the Bill & Melinda Gates Foundation and the Wellcome Trust.
What is postpartum haemorrhage?
Postpartum bleeding or postpartum haemorrhage (PPH) is often defined as the loss of more than 500 ml (at vaginal birth) or 1,000 ml (at caesarean section) of blood within the first 24 hours following childbirth.
Excessive bleeding after childbirth, usually known as PPH is a leading cause of maternal mortality and morbidity. PPH follows 6% to 10% of all births and accounts for around 100,000 maternal deaths every year. Ninety-nine percent of deaths are in low and middle income countries (LMICs). Many women who survive experience severe morbidity. Some women need surgery to control the bleeding (e.g. exploratory laparotomy, uterine artery ligation, brace sutures) and many require a hysterectomy, thus removing the possibility of having more children. Severe morbidity due to PPH interferes with breastfeeding and bonding.
The WOMAN-2 trial will provide reliable evidence on the effect of tranexamic acid (TXA) on preventing PPH.
What is tranexamic acid?
The WOMAN-2 trial is testing tranexamic acid (or TXA), a blood clot stabiliser that was discovered in Japan in the 1950’s, to see if it can prevent excessive bleeding soon after giving birth. TXA is a widely available medicine that is commonly used for other bleeding conditions and works by maintaining the blood clots that prevent bleeding.
The ability to form a blood clot depends on fibrinogen levels. In both trauma and PPH, a low serum fibrinogen is a strong predictor of life threatening bleeding. Early TXA administration has the potential to prevent excessive blood loss by reducing fibrinogen depletion. Women with anaemia are at increased risk of bleeding soon after delivery. If they can be treated with TXA before their fibrinogen levels fall, severe postpartum bleeding and its consequences may be prevented.
Anaemia and postpartum haemorrhage
Anaemia is a cause and consequence of PPH. A cohort study in Assam, India found that women with moderate or severe anaemia had a greatly increased risk of PPH (1). Women with moderate anaemia had a 50% increased risk of PPH, whereas those with severe anaemia had a ten-fold increased risk. The reasons for the increased risk is unclear but some researchers think that anaemic women are more susceptible to uterine atony due to impaired oxygen transport to the uterus.
Anaemic women experience worse outcomes after PPH. An international survey of 275,000 women found that severe maternal outcomes after PPH were nearly three times more common in anaemic than in non-anaemic women (2).
Even moderate bleeding can be life threatening in anaemic women. Excessive bleeding after childbirth worsens maternal anaemia, raising the possibility of a vicious circle of bleeding and adverse outcomes. Fatigue due to anaemia limits a mother’s wellbeing and her ability to care for her children (3).
Despite efforts to prevent anaemia, many women labour with low haemoglobin levels. Worldwide, over one-third of pregnant women are anaemic and many are severely anaemic (4). The prevalence is highest in countries in central and West Africa as well as in South Asia where about half of pregnant woman are anaemic and it poses a severe public health problem (4, 5).
There is an urgent need to find an effective way to reduce postpartum bleeding in anaemic women.
- Nair M, Choudhry MK, Choudhry SS, Kakoty SD, Sarma UC, Webster P, et al. Association between maternal anaemia and pregnancy outcome: a cohort study in Assam, India. BMJ Global Health. 2016;1(e000026).
- Sheldon WR, Blum J, Vogel JP, Souza JP, Gulmezoglu AM, Winikoff B, et al. Postpartum haemorrhage management, risks, and maternal outcomes: findings from the World Health Organization multicountry survey on maternal and newborn health. BJOG 2014;121 suppl 1:5-13.
- Geller S, Adams M, Kelly P, Kodkany B, Derman R. Postpartum haemorrhage in resource-poor settings. International Journal of Gynecology and Obstetrics 2006;92:202-211.
- Stevens GA, Finucane MM, De-Regil LM, Paciorek CJ, Flaxman SR, Branca F, et al. Global, regional, and national trends in haemoglobin concentration and prevalence of total and severe anaemia in children and pregnant and non-pregnant women for 1995-2011: a systematic analysis of population-representative data. Lancet Glob Health 2013;1(1):e16-25.
- WHO. Global prevalence of anaemia in 2011. http://apps.who.int/iris/bitstream/10665/177094/1/9789241564960_eng.pdf 2008.