Point of view from the JSI PPH working group
In 2015, more than 300, 000 women died in childbirth. The vast majority of these deaths could have been prevented.1 Postpartum hemorrhage (PPH) is the leading cause of maternal death, and accounts for an estimated 19 percent of maternal deaths.2 Who will hemorrhage after delivery is unpredictable but if untreated, PPH can kill a woman within 2 hours.3
The primary recommendation to treat PPH is oxytocin and other uterotonics. One course of action is the drug tranexamic acid (TA), although WHO in 2012 made a “weak recommendation” for using TA to prevent and treat PPH, based on “moderate quality evidence.” The guidelines further recommend that TA should be used only “if oxytocin and other uterotonics fail to stop the bleeding, or if it is thought that the bleeding may be partly due to trauma.”4
A more recent study, published in the Lancet in April 2017, has strengthened the evidence base on the effectiveness of TA. With a sample size of 20,060 women experiencing PPH in 21 countries, the authors have demonstrated that administering 1 gram of intravenous TA decreases the risk of death from blood loss associated with childbirth by about 20 percent; it is even more protective if administered within three hours of giving birth. As a result, the authors suggest that TA be given alongside uterotonics.5
Given this recent evidence, JSI—which currently implements maternal health projects in 24 countries—has debated the value of promoting the use of tranexamic acid for PPH. Although the cost of the drug is not prohibitive, there are a number of issues that should be considered before TA can be administered safely to women who might need it.
Potential study weaknesses in the most recent evidence base:
- Fifty-five percent of study participants were from Nigeria and Pakistan; this potentially introduces biological variations (i.e., anemia prevalence) that may affect the risk of PPH, and geographical locations were not adjusted for in the analyses.
- Although study participants all had a clinical diagnosis of PPH, the methodology for measuring blood loss was inexact.
Challenges in administering the intravenous TA in resource-poor settings:
- As the authors note, in low- and middle-income countries, most deaths from PPH occur at home or in settings where the prerequisites for safe intravenous injections are not feasible.6
- The approach to intravenous TA (1g delivered by slow intravenous injection over ten minutes) mandates that providers are skilled and able to administer the drug at the required rate.
- Recent evidence suggests that TA is most effective when administered within three hours of the onset of PPH. Getting PPH patients to a facility that has the capacity to deliver TA safely within that timeframe is often difficult in many of the countries where JSI works.
- TA is available in tablet form.a Although the efficacy of TA ingestion on PPH has not been assessed, the delay in absorption may make it an inappropriate treatment for PPH. This is an area for further research.
Tranexamic acid has been shown to reduce deaths due to PPH, and we commend all efforts to identify ways to improve maternal health outcomes and ultimately achieve Sustainable Development Goal 3.1.b However, the conditions necessary to deliver TA safely currently preclude it from treating women with PPH in the resource-poor settings where JSI works.
- Estimates by WHO, UNICEF, UNFPA WBG, and the United Nations Population Division. Trends in Maternal Mortality: 1990 to 2015. http://apps.who.int/iris/bitstream/10665/194254/1/9789241565141_eng.pdf?ua=1. Accessed May 31, 2017.
- Say L, Chou D, Gemmill A, et al. Global causes of maternal death: a WHO systematic analysis. Lancet Glob Heal. 2014;2(6):e323-e333. doi:10.1016/S2214-109X(14)70227-X.
- Walraven G, Telfer M, Rowley J, Ronsmans & C. Maternal mortality in rural Gambia: levels, causes, and contributing factors. http://www.who.int/bulletin/archives/78(5)603.pdf. Accessed May 24, 2017.
- WHO recommendations for the prevention and treatment of postpartum haemorrhage. http://apps.who.int/iris/bitstream/10665/75411/1/9789241548502_eng.pdf. Published 2012. Accessed May 4, 2015.
- Shakur H, Roberts I, Fawole B, et al. 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. doi:10.1016/S0140-6736(17)30638-4.
- WOMAN: reducing maternal deaths with tranexamic acid. Lancet (London, England). 2017;389(10084):2081. doi:10.1016/S0140-6736(17)31111-X.
aTA is available in 500 mg tablets, often used to treat nosebleeds and heavy periods. The tablets are heat-stable up to 25 degrees Celsius and have a half-life of 3 hours.
bSDG TARGET 3.1: Reduce the global maternal mortality ratio to less than 70 per 100,000 live births by 2030.