In 2017 WHO added TXA to its Postpartum Hemorrhage Recommendations

The WOMAN Trial (World Maternal Antifibrinolytic Trial) was an international randomized double-blind, placebo controlled trial that began in 2010 to investigate the effect of early administration of tranexamic acid on morbidity, mortality, and hysterectomy. The trial involved over 20,000 females diagnosed with postpartum hemorrhage across 21 countries and found that tranexamic acid significantly reduced death due to blood loss when administered within 3 hours after the patient gives birth.

In August of 2017, the World Health Organization updated their recommendation on the use of tranexamic acid to support the use of 1 g intravenous tranexamic acid within 3 hours of childbirth in females with postpartum hemorrhage. 

The WOMAN trial found that the administration of intravenous tranexamic acid in patients with postpartum hemorrhage led to a 21% decrease in mortality from blood loss and a 29% decrease in mortality.  Note that the WOMAN trial only looked at intravenous administration of TXA-- in order to be widely available in lower resource settings oral or topical applications of TXA will require evaluation in separate trials. 

Tranexamic acid is a medication invented in 1962 by Utako and Shosuke Okamoto that prevents excessive bleeding. The human body naturally breaks down blood clots to prevent unnecessary and excessive clotting, which can cause vascular dysfunction. However during childbirth, the breakdown of blood clots could lead to dangerous levels of blood loss, such as in the case of postpartum hemorrhage. Tranexamic acid is an indirect fibrinolytic inhibitor, meaning that it can prevent the breakdown of blood clots, which can prevent a patient from bleeding out. 

Tranexamic acid was first put into practice to aid in curbing excessive blood loss in those that suffer from excessive menstrual bleeding and bleeding disorders. It is now also used in elective surgeries and undergoing clinical trials in the use of tranexamic acid in cardiac surgeries. 

Utako and Shosuke Okamoto had initially developed tranexamic acid decades ago to treat and prevent postpartum hemorrhage, but obstetricians would not perform the clinical trials to test the drug’s efficacy. The lack of clinical trials made it impossible for tranexamic acid to be used to treat postpartum hemorrhage, but eventually its success with excessive menstrual bleeding and bleeding disorders with few contraindications and adverse side effects garnered enough trust that clinical trials began for the use of tranexamic acid in cases of postpartum hemorrhage and in cardiac surgeries. 

Although Utako and Shosuke Okamoto did not live to see the WHO 2017 update, their pharmacological innovation has saved thousands of lives, a number which will continue to grow into the future.  Follow-on clinical trials like the TRAAP2 study are delving into the use of TXA in specific clinical situations like cesarean section.  The WOMAN-PharmacoTXA trial is assessing the pharmacokinetics and pharmacodynamics of intramuscular, intravenous and oral administration of TXA.  Maternova will be following the results of all of these clinical trials and reporting in this blog.

By Julia Doo and Meg Wirth

Sources 

Image: London School of Hygiene and Tropical Medicine

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Written by Julia Doo