The results of a recent international trial confirm that administration of tranexamic acid significantly reduces mortality due to bleeding from post-partum haemorrhage, without any increase in adverse events. The treatment is more effective if tranexamic acid is administered as soon as possible after the onset of bleeding.
Post-partum haemorrhage, defined as excessive bleeding following the birth of a baby, is the leading cause of maternal death worldwide. Post-partum haemorrhage occurs right after birth but in some cases, can occur later as well. Mortality due to post-partum haemorrhage is highest (almost 99%) in low-income and middle-income countries.
Tranexamic acid inhibits enzymatic breakdown of fibrinogen and fibrin by plasmin, thereby reducing bleeding. Evidence from previous trials shows that tranexamic acid can reduce death due to bleeding in trauma patients if given within 3 hours of injury. In 2012, the World Health Organization (WHO) recommended the use of tranexamic acid for treatment of post-partum haemorrhage when bleeding is thought to be due to trauma. However, this recommendation was extrapolated from evidence provided by trials conducted in surgery and trauma patients (CRASH-2 trial).
The WOMAN (World Maternal Antifibrinolytic) trial, conducted between March 2010 and April 2016 by the London School of Hygiene and Tropical Medicine, included 20,000 women aged 16 years and older with a clinical diagnosis of post-partum haemorrhage after a vaginal birth or a caesarian section. The trial was randomized, double-blind, placebo-controlled and data was collected from 193 hospitals in 21 countries. Women were randomly assigned to receive 1 gram intravenous tranexamic acid or matching placebo. A second dose of 1 gram tranexamic acid was given if bleeding continued after 30 minutes or stopped and restarted within 24 hours of the first dose. The primary outcome was a composite of death from all causes or hysterectomy within 42 days of randomization.
The results, based on the effects of treatment on primary outcome, were divided into three characteristics: type of birth (vaginal or caesarian section), hours from giving birth to randomization, and primary cause of haemorrhage (uterine atony vs all other).
There were 483 maternal deaths, of which 374 were within 24 hours of randomization and 43 were within 1 hour of randomization. In women who were given tranexamic acid within 3 hours of giving birth, there was a significantly reduced risk of death due to bleeding. A total of 89 women died in tranexamic group vs 127 in the placebo group. However, there was not a significant difference between two groups when treatment was given after 3 hours. These results were not affected by type of birth or cause of bleeding. In addition, the incidence of any adverse events also did not differ significantly between the tranexamic and placebo group.
The WOMAN trial results clearly show that administration of tranexamic acid to women reduces death due to bleeding in cases of post-partum haemorrhage without any complications of adverse effects. If treatment is given soon after delivery, tranexamic acid can reduce death due to bleeding by almost one third. Although treatment with tranexamic acid did not prevent hysterectomy, it significantly reduced the number of laparotomies to control bleeding.
A high proportion of mothers die within hours of onset of post-partum haemorrhage. In such a situation, waiting to see if uterotonics helps to stop bleeding may put the mother’s life at risk. Therefore, early administration of tranexamic acid is most effective in reducing death due to bleeding as well as the need for laparotomy to control bleeding.
In developed countries, hysterectomy is the last resort to control bleeding, however, in some developing countries where many women are anemic and blood supplies are limited, hysterectomy is usually done as an early intervention to prevent death due to bleeding. The use of tranexamic acid can prevent death and hysterectomy in these cases. Furthermore, many deaths due to post-partum bleeding in low income and middle-income countries occur at home or a place where intravenous injections are not available. Further research is needed to assess non-intravenous use and bioavailability of tranexamic acid where intravenous injections cannot be used.
Written By: Preeti Paul, MS Biochemistry