Prophylactic Tranexamic Acid Cuts Postpartum Hemorrhage Risk in Repeat Cesarean Sections

Postpartum hemorrhage remains one of the most feared complications in obstetrics, a condition in which the uterus fails to clamp down on bleeding after delivery and a mother can lose more than a liter of blood within hours. For women undergoing their second, third, or subsequent cesarean section, the danger is amplified: scarred uterine tissue, peritoneal adhesions from previous surgeries, and impaired uterine contraction all conspire to raise bleeding risk well above that of a first cesarean delivery. Now, a large retrospective cohort study from a tertiary obstetrical center in South China offers some of the most targeted real-world evidence to date that a single gram of prophylactic tranexamic acid, given intravenously during repeat cesarean sections, can substantially reduce the incidence of this dangerous complication.

The research, conducted at Guangzhou Women and Children’s Medical Center affiliated with Guangzhou Medical University and published in Frontiers in Drug Safety and Regulation, analyzed medical records from 16,952 women who underwent repeat cesarean sections between July 2016 and December 2023. Of these, 2,777 women received prophylactic tranexamic acid intraoperatively, while the remaining 14,175 did not. Because the decision to administer the drug was left to the clinical judgment of attending obstetricians rather than a standardized protocol, the researchers faced an immediate statistical challenge: the two groups differed systematically in baseline characteristics, including rates of gestational hypertension and general anesthesia use. To address this imbalance, the team employed 1:2 propensity score matching with a caliper of 0.01, a technique that pairs each treated patient with two untreated patients who have nearly identical predicted probabilities of receiving the drug based on maternal age, pre-pregnancy body mass index, gestational age, gestational diabetes, gestational hypertensive disorders, neonatal birth weight, and other covariates.

After matching, 2,777 women in the tranexamic acid group were compared with 5,554 women in the control group, and the standardized mean differences for all covariates fell below 0.10, indicating that the matched cohorts were well balanced. The results were striking. The incidence of postpartum hemorrhage, defined as estimated blood loss of at least 1,000 milliliters within 24 hours of cesarean section or red blood cell transfusion within two days of delivery, was 11.09 percent in the tranexamic acid group compared with 17.03 percent in the control group, a difference that was highly statistically significant with a P value below 0.001. In absolute terms, this means roughly six additional cases of postpartum hemorrhage were prevented for every 100 women treated.

Secondary outcomes reinforced the primary finding. Women who received prophylactic tranexamic acid showed a smaller postpartum hemoglobin decline, with 12.06 percent experiencing a drop of at least 20 grams per liter compared with 18.44 percent in the control group. Calculated estimated blood loss categories also favored the treated group: 38.6 percent of women in the tranexamic acid group had calculated blood loss exceeding 500 milliliters, compared with 49.51 percent of controls, and only 9.94 percent exceeded 1,000 milliliters versus 15.72 percent of controls. The rate of additional uterotonic agents, specifically intramuscular carboprost tromethamine, was also lower in the treated group at 26.9 percent versus 29.8 percent, suggesting that tranexamic acid reduced the reliance on second-line, more potent uterotonics that carry greater side effect profiles.

Multivariate logistic regression, adjusting for age, gestational age, body mass index, general anesthesia, gestational hypertensive disorders, gestational diabetes, and macrosomia, confirmed that prophylactic tranexamic acid was an independent protective factor against postpartum hemorrhage, with an odds ratio of 0.620 and a 95 percent confidence interval of 0.540 to 0.712. This means that, even after accounting for measurable confounders, women who received the drug had roughly 38 percent lower odds of experiencing postpartum hemorrhage than matched controls who did not.

Notably, the study found no statistically significant difference in blood transfusion rates between the two groups, with 1.55 percent of the tranexamic acid group requiring transfusion compared with 2.09 percent of controls, a P value of 0.089. The researchers attribute this to their center’s strict adherence to restrictive transfusion thresholds, following national guidelines that recommend transfusion only when hemoglobin falls below 70 grams per liter or when symptomatic anemia is present. Because transfusions were already rare in both groups, the study lacked the statistical power to detect a difference in this particular outcome, a limitation shared with several large randomized trials of tranexamic acid in obstetrics.

Tranexamic acid is an antifibrinolytic agent that works by blocking the conversion of plasminogen to plasmin, thereby inhibiting the breakdown of fibrin clots. In trauma surgery and other bleeding scenarios, the drug has demonstrated mortality benefits in landmark trials such as CRASH-2. In obstetrics, the World Health Organization recommends early intravenous tranexamic acid for patients with confirmed postpartum hemorrhage, but the evidence for prophylactic use during cesarean section has been more complex and evolving. While numerous small-to-medium-sized randomized controlled trials and meta-analyses have suggested that the drug reduces blood loss and transfusion requirements, the certainty of this evidence has been graded as low due to serious limitations in trial design and reporting. More importantly, recent large-scale pragmatic randomized trials have yielded mixed or null findings regarding clinically significant outcomes.

The TRAAP2 trial, a multicenter double-blind randomized controlled trial involving over 11,000 women undergoing cesarean delivery, found that while tranexamic acid reduced a composite outcome of calculated blood loss exceeding 1,000 milliliters or red cell transfusion, it did not significantly reduce the need for additional uterotonics or other clinically relevant hemorrhagic morbidity. Another major randomized trial similarly found no significant reduction in a composite of hemorrhage-related outcomes with prophylactic tranexamic acid. The new Chinese cohort study, focused specifically on the repeat cesarean subgroup, found reductions in both calculated blood loss and additional uterotonic use, a discrepancy the researchers attribute to population specificity. Women with prior uterine scars face heightened bleeding risk from both uterine atony and surgical wound oozing, and tranexamic acid’s antifibrinolytic action may be particularly effective against the latter mechanism, potentially yielding greater relative benefit in this subgroup than in an unselected cesarean population.

Safety considerations are paramount when evaluating any prophylactic intervention in pregnancy. The researchers observed no thromboembolic events in their cohort, consistent with the short-term safety profile reported in many studies of tranexamic acid. However, they caution that the retrospective nature of the study, the lack of active surveillance for thromboembolism, and the relatively low incidence of these events in the general obstetric population limit their ability to draw definitive conclusions about safety. Large trials have reported small numerical increases in thromboembolic events with tranexamic acid, as well as increased incidences of non-thromboembolic adverse effects such as nausea and vomiting, which retrospective data did not capture. The researchers emphasize that ongoing vigilance and prospective safety data collection, specifically in high-risk obstetric subgroups, remain essential.

The study also noted a counterintuitive finding: a significantly higher rate of severe hemorrhage-related interventions, including arterial embolization, hysterectomy, or emergency surgery, in the tranexamic acid group at 0.5 percent versus 0.18 percent in controls. The researchers propose that this may be a statistical artifact due to the very small number of events, or that when postpartum hemorrhage did occur in the treated group, it may have been more severe or refractory to medical management. Given the small numbers involved, they emphasize that this finding should be considered hypothesis-generating and requires further investigation in larger, prospective studies. The authors conclude that prophylactic tranexamic acid was associated with a lower incidence of postpartum hemorrhage and reduced need for additional uterotonics in women undergoing repeat cesarean sections, and they call for dedicated randomized controlled trials in this specific high-risk population to confirm these hypothesis-generating findings.

Subject of Research: Maternal-Fetal Medicine

Article Title: Efficacy of prophylactic tranexamic acid in preventing postpartum hemorrhage following repeat cesarean sections: a retrospective matched-cohort study

Article References: Di, X., Li, X., Zheng, Z., Guo, L., Dong, T., & Chen, Q. (2026). Efficacy of prophylactic tranexamic acid in preventing postpartum hemorrhage following repeat cesarean sections: a retrospective matched-cohort study. Frontiers in Drug Safety and Regulation, 6, Article 1911287. https://doi.org/10.3389/fdsfr.2026.1911287

Image Credits: AI Generated

DOI: 10.3389/fdsfr.2026.1911287

Keywords: tranexamic acid, postpartum hemorrhage, repeat cesarean section, propensity score matching, maternal health, obstetrics, antifibrinolytic, Frontiers in Drug Safety and Regulation, Efficacy, prophylactic, tranexamic, acid