Background
Postpartum hemorrhage (PPH) is the leading global cause of maternal morbidity and mortality. Tranexamic acid (TXA), an antifibrinolytic agent that has been shown to reduce hemorrhage-related mortality in trauma, is used off-label for the prevention and treatment of PPH, typically in conjunction with uterotonic agents. If TXA is effective in the prevention and management of PPH, this inexpensive medication could improve PPH care and reduce PPH-related morbidity and mortality. The majority of evidence on TXA use for PPH prevention and treatment comes from studies conducted in low- and middle-income countries (LMICs) and may be of less relevance to the U.S. or other high-income contexts.
Objective
To review recent, high-quality evidence on the use of tranexamic acid (TXA) for the prevention and treatment of postpartum hemorrhage (PPH) in high-income countries (HICs).
Study Design
We searched databases including PubMed, CINAHL, EMBASE, Web of Science, and SCOPUS for recent evidence on the use of TXA for prevention or treatment of PPH. Searches were limited to English-language records of human subjects published between January 2019 and February 2025. Supplementary searches of the grey literature, including Advanced Google Scholar and ClinicalTrials.gov, were also conducted. We used explicit inclusion and exclusion criteria determined a priori following the PECOTS framework. Publication types were restricted to completed randomized controlled trials (RCTs) meeting minimum sample size criteria in their reporting. We also included recent large seminal trials that included HICs in their study population even if they were published prior to January 2019.
Results
We identified thirteen recent RCTs conducted in HICs; 3 of these met sample size requirements, and all focused on the use of TXA for PPH prevention. No large RCTs focused exclusively on the use of TXA for PPH treatment in HICs. Studies included a mix of cesarean (2 RCTs) and vaginal (1 RCT) deliveries.Only 2 new, large trials (both on PPH prevention in cesarean deliveries) were published within the last five years. These 2 studies conflicted on whether TXA prevents PPH: the larger RCT (conducted in the U.S.) showed no reduction in PPH (≥1,000 mL or greater blood loss), and the smaller RCT (TRAAP2 trial, conducted in France) showed that TXA reduced the incidence of PPH overall, and reduced estimated blood loss but not gravimetrically estimated blood loss. However, neither study found TXA effective for preventing clinical outcomes associated with PPH, including the rate of blood transfusions, use of surgical interventions, or ICU admissions. The third RCT (TRAAP trial, conducted in France) was published in 2018 and found that TXA was not effective at preventing PPH, including the rate of blood transfusions and the use of surgical interventions, after vaginal deliveries.
Conclusion
Recent, high-quality RCT evidence on the use of TXA in PPH care in high-income countries has shown limited, if any, effectiveness of TXA for PPH prevention in vaginal or cesarean deliveries.
