Tranexamic acid for the prevention of blood loss after cesarean section: an updated systematic review and meta-analysis of randomized controlled trials

Objective: Tranexamic acid (TXA) is a cost-effective intervention for the prevention of postpartum hemorrhage (PPH) in women undergoing cesarean section but the evidence to support its use is conflicting. We conducted this meta-analysis to evaluate the efficacy and safety of TXA in low- and high-risk cesarean deliveries. Data sources: We searched MEDLINE (via PubMed), Embase, the Cochrane Library, ClinicalTrials.gov, and WHO International Clinical Trials Registry Platform (ICTRP) portal from inception to April 2022 (updated October 2022 and February 2023) with no language restrictions. Additionally, grey literature sources were also explored. Study eligibility criteria: All randomized controlled trials (RCTs) investigating the prophylactic use of intravenous TXA in addition to standard uterotonic agents in women undergoing cesarean deliveries as compared to placebo, standard treatment, or prostaglandins were included in this meta-analysis. Methods: We used the revised Cochrane "Risk of Bias" tool (RoB 2.0) to assess the quality of included RCTs. RevMan 5.4 was used to conduct all statistical analyses under a random-effects model. Results: We included 50 RCTs (6 in only high-risk patients and 2 with prostaglandins as the comparator) evaluating TXA in our meta-analysis. TXA reduced the risk of blood loss >1000 mL, mean total blood loss, and the need for blood transfusion in both low- and high-risk patients. TXA was associated with a beneficial effect in our secondary outcomes including decline in hemoglobin levels and the need for additional uterotonic agents. TXA increased the risk of non-thromboembolic adverse events but, based on limited data, did not increase the incidence of thromboembolic events. The administration of TXA before skin incision, but not after cord clamping, was associated with a large benefit. The quality of evidence was rated as low to very low for outcomes in the low-risk population and moderate for most outcomes in the high-risk subgroup. Conclusions: TXA may reduce the risk of blood loss in cesarean deliveries with a higher benefit observed in high-risk patients but the lack of high-quality evidence precludes any strong conclusions. Additional studies, especially in the high-risk population and evaluating the timing of TXA administration, are needed to confirm or refute these findings.