Postpartum hemorrhage significantly contributes to maternal mortality worldwide, with obstetrical hemorrhage being the second leading cause of pregnancy-related death in the United States. Tranexamic acid, a fibrinolysis inhibitor, has reduced overall mortality in patients with bleeding trauma, traumatic brain injury, and established obstetrical hemorrhage. The increase in fibrinolytic activity after the delivery of the placenta has led to the use of tranexamic acid to prevent obstetrical hemorrhage.
Still, previous studies have been limited by small sample sizes and a lack of power to evaluate critical clinical outcomes. In this context, two large, multicenter clinical trials have investigated the prophylactic use of tranexamic acid to prevent hemorrhage after vaginal or cesarean delivery, with mixed results.
A new study published in the New England Journal of Medicine has found that the prophylactic use of intravenous tranexamic acid immediately after umbilical cord clamping did not lead to a significantly lower risk of maternal death or blood transfusion among patients undergoing scheduled or unscheduled cesarean delivery. The study was a randomized trial involving patients undergoing either scheduled or unscheduled cesarean delivery. The researchers did not find a material between-group difference in the incidence of estimated intraoperative blood loss of more than 1 liter.
Treatments and surgical interventions in response to bleeding and related complications occurred in 16.1% of the tranexamic acid group participants and 18.0% of those in the placebo group. Although the findings suggest the possibility that prophylactic tranexamic acid may have led to a lower risk of interventions in response to bleeding and related complications, the apparent between-group difference was accounted for by less use of uterotonic agents in the tranexamic acid group than in the placebo group. There were no substantial between-group differences in surgical or interventional radiologic procedures. Moreover, any benefit did not translate to fewer blood transfusions.
The risk of thromboembolic events (venous or arterial) was not higher in the tranexamic acid group than in the placebo group. In cases where open-label tranexamic acid was used, the protocol allowed for only the intravenous administration of 1 g of tranexamic acid within the first 24 hours after the trial infusion was completed. Therefore, participants should have received at most 2 g of tranexamic acid within 24 hours. The safety of higher doses requires further study. The incidence of postpartum infection was 3.2% in the tranexamic acid group and 2.5% in the placebo group.
The findings of this study are inconsistent with those of previous observational studies and systematic reviews suggesting that prophylactic tranexamic acid during cesarean delivery reduces the use of blood transfusion. Many of these trials were small, single-center studies prone to biases, and none were adequately powered to evaluate the use of blood transfusion.
A recent large, randomized, placebo-controlled trial also showed no significant difference in the use of blood transfusion with prophylactic administration of tranexamic acid during cesarean delivery. Still, that trial was not powered to detect a difference in the incidence of transfusion.
Another limitation of the previous trial was that approximately 70% of the patients underwent cesarean delivery before the onset of labor, a situation associated with a lower risk of bleeding and use of blood transfusion than cesarean delivery performed during labor. The authors found no between-group difference in the use of uterotonic agents. Still, they did find that the calculated blood loss was significantly less in the tranexamic acid group than in the placebo group (mean difference, approximately 100 ml).