Prophylactic use of tranexamic acid to prevent postpartum hemorrhage in high-risk cesarean deliveries: a systematic review and meta-analysis

Prophylactic use of tranexamic acid to prevent postpartum hemorrhage in high-risk cesarean deliveries: a systematic review and meta-analysis | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Systematic Review Prophylactic use of tranexamic acid to prevent postpartum hemorrhage in high-risk cesarean deliveries: a systematic review and meta-analysis Xochitl Sandoval López, Hazel C. García, Cesar M. Gavidia, Karina V. Alam, and 2 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-7961244/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract Background . Postpartum hemorrhage is a leading cause of maternal morbidity and mortality worldwide, particularly among high-risk women. Tranexamic acid has been used as prophylaxis for postoperative blood loss. This systematic review and meta-analysis evaluated the efficacy and safety of tranexamic acid in preventing postpartum hemorrhage in cesarean sections in high-risk women. Methods . A systematic review with meta-analysis was performed. The risk of bias was assessed using RoB 2.0. Meta-analyses were performed using a random-effects model, along with subgroup and sensitivity analyses. The GRADE methodology was used to assess the certainty of the evidence. Results . Ten randomized controlled trials involving 1,811 participants were included. Tranexamic acid substantially reduced total blood loss (SMD = -1.74; 95% CI -3.09 to -0.39), with optimal efficacy when administered 15–20 minutes before incision (SMD = -0.61; 95% CI -0.82 to -0.39). Intraoperative blood loss (SMD = -0.99; 95% CI -1.15 to -0.82), blood loss at two hours (SMD = -0.78; 95% CI -1.21 to -0.35), and blood loss >1000 mL (RR = 0.24; 95% CI 0.14 to 0.41) were also reduced. Hematological outcomes, need for additional uterotonics (RR = 0.37; 95% CI 0.24 to 0.58), blood transfusions (RR = 0.30; 95% CI 0.22 to 0.40), and complementary surgical interventions (RR = 0.35; 95% CI 0.16 to 0.78) were likely reduced. Conclusions . Tranexamic acid as a prophylactic intervention effectively reduces blood loss in high-risk cesarean sections, particularly when administered 15–20 minutes before skin incision. It decreases total and intraoperative blood loss, blood loss at two hours, and cases exceeding 1000 mL. Tranexamic acid also likely reduces postoperative hemoglobin and hematocrit drops, the need for additional uterotonics, blood transfusions, and complementary surgical interventions. Trial registration. PROSPERO CRD420251087054. Maternal & Fetal Medicine Postpartum Hemorrhage Tranexamic Acid Cesarean Section High Risk Pregnancy Figures Figure 1 Figure 2 Figure 3 Figure 4 Background Postpartum hemorrhage (PPH) is one of the leading causes of maternal morbidity and mortality worldwide and is particularly relevant in women who have undergone cesarean section (C-section).[ 1 ] This type of hemorrhage is defined as blood loss exceeding 1000 mL after delivery or accompanied by symptoms or signs of hypovolemia within 24 hours after birth,[ 2 ] which can lead to serious complications or death.[ 3 ] Despite medical advances, the PPH continues to be a challenge in obstetrics, with direct implications for maternal health and healthcare costs.[ 4 ] Globally, the proportion of cesarean deliveries is increasing,[ 5 ] accounting for approximately 30% of deliveries in developed countries and 20% of all deliveries worldwide.[ 6 ] It is estimated that between 1% and 5% of these procedures may be complicated by PPH.[ 7 ] Maternal mortality attributed to PPH remains high in some regions,[ 8 ] with the prevalence varying by region, ranging from 2.4% to 12.1%.[ 9 ] Women considered at high risk are more likely to suffer from PPH due to factors such as a history of hemorrhage, multiple pregnancies, placenta previa, or placental abruption, among others. In this context, tranexamic acid (TXA) has emerged as an essential option for reducing PPH in women undergoing C-section.[ 10 ] TXA is an antifibrinolytic agent that can help control excessive blood loss.[ 11 ] Its use has become widespread in various surgical and trauma settings, and it has been proposed as a prophylactic intervention for PPH.[ 9 ] However, evidence of its efficacy compared with that of placebo or standard treatment remains under investigation.[ 12 ] Therefore, this systematic review aims to evaluate the efficacy and safety of TXA for the prevention of PPH in women undergoing C-section and compare its use with that of placebo or standard treatment. Methods Study design A systematic review with meta-analysis was conducted following the recommendations of the PRISMA 2020 statement. This protocol has been registered in the PROSPERO database with the registration number 2025 CRD420251087054. Available at: https://www.crd.york.ac.uk/PROSPERO/view/CRD420251087054 . Searches A systematic search was conducted in the PubMed, Scopus, Web of Science, EMBASE, CINAHL, Cochrane Library, ClinicalTrials.gov, and International Clinical Trials Registry Platforms of the World Health Organization databases from their inception to July 3, 2025. For each database, a tailored search strategy was applied, using free-text terms in all cases, the Medical Subject Headings thesaurus in PubMed, and the Emtree thesaurus in EMBASE and Scopus. The main search terms included "postpartum hemorrhage", "tranexamic acid", "cesarean section", and "high-risk pregnancy". No language or publication date restrictions were applied. Eligibility criteria All randomized controlled trials that evaluated pregnant women and compared TXA prophylaxis with placebo or standard treatment were included. Studies included women aged 18 years or older with medical or obstetric conditions associated with a high risk of hemorrhage. Studies involving women with hypersensitivity to TXA, hematological disorders with a predisposition to bleeding, a history of thromboembolism, or ongoing anticoagulant treatment were excluded. Outcomes The primary outcomes were total blood loss, defined as the estimated volume of blood loss at the end of the study; total blood loss at two hours, which corresponds to the volume lost during delivery and the two hours following delivery; and the incidence of postpartum hemorrhage, defined as a loss of more than 1000 mL or the need for red blood cell transfusion within two days after delivery. The secondary outcomes included changes in hemoglobin and hematocrit; clinical and laboratory variables related to blood loss; adverse events; the length of hospital stay; the need for blood transfusion; and additional uterotonics, which were systematically documented. Selection process The records obtained from the electronic searches were exported to EndNote, where they were consolidated into a library, and duplicates were removed. The library was then uploaded to Rayyan for initial screening by title and abstract. Studies selected in the initial screening were evaluated in full text for a new review process. Eligible studies were included in the review, and the data extraction process was performed. This stage was assessed blindly and independently by the reviewers. Conflicts were resolved at each stage by team consensus. Data extraction Data from each study were extracted individually via a predesigned format in a Microsoft Excel spreadsheet. For each analysis, information was collected on the author, year of publication, country, type of study, number of participants per intervention group, mean age per group, eligibility criteria, and description of the intervention and control, as well as primary and secondary outcomes. Assessment of risk of bias The risk of bias was assessed via the RoB 2.0 tool by the reviewers. RoB was classified by domain as low, with some concerns, or high. Disagreements were resolved through discussion with a sixth reviewer (XSL). Data synthesis The meta-analysis was performed via a random effects model, and the inverse variance method was used to estimate the effects of TXA compared with those of the placebo. The variance between studies (tau²) was estimated via the Paule‒Mandel method. Continuous outcomes were analyzed via mean differences (MDs) or standardized mean differences (SMDs), as appropriate, accompanied by 95% confidence intervals (95% CIs). For dichotomous outcomes, the effect was quantified using the relative risk (RR) with 95% CI. In studies with no events in one or both groups, a continuity correction was applied. The confidence intervals were adjusted via the Hartung‒Knapp‒Sidik‒Jonkman method for meta-analyses with more than five studies or the profile likelihood method for those with five or fewer studies. Heterogeneity between studies was assessed via the I² statistic, considering low ( 60%) levels. Heterogeneity was explored via subgroup analysis. For sensitivity analysis, meta-analyses were performed, excluding studies with high heterogeneity or with specific characteristics that could influence the results. The analysis was performed in R v4.4.2 via the metabin function of the meta package. GRADE assessment The certainty of the evidence and the level of recommendation were assessed via the GRADE methodology, which considers the domains of risk of bias, inconsistency, indirect evidence, imprecision, and publication bias. The assessment was performed for each outcome and summarized in summary of evidence (SoE) tables, developed via the online software GRADEpro GDT. Results A total of 1811 articles were identified in five databases, of which 1006 duplicates were removed. After duplicate removal, 805 articles were screened by title and abstract, and 740 were excluded because they did not meet the inclusion criteria. Sixty-five full-text articles were analyzed, and 55 were discarded because of an incorrect study design (n = 16), an incorrect population (n = 6), an unavailable full-text paper (n = 4), unpublished results (n = 13), an incorrect publication type (n = 14), or an incorrect outcome (n = 2). Finally, 10 randomized clinical trials (n = 1854) were included for qualitative and quantitative analyses.[ 13 – 22 ] (Fig. 1). Figure 1. PRISMA 2020 flow chart. Characteristics of participants and included studies Ten randomized clinical trials were published between 2019 and 2025 and were conducted in some regions of the world, including Asia and Africa. The number of participants in the studies ranged from 50–200 women. No significant differences were observed in the mean age between groups within studies or when comparisons were made among studies (p < 0.05). Blood loss was estimated via the weighing of surgical drapes and towels (gravimetric method) and two formula-based calculations: estimated blood loss (EBL) and the Nadler formula. The follow-up period was 24 to 48 hours in most studies, with some studies extending to four or six weeks (Table 1 ). Table 1 Characteristics of the included studies Author Country/Region Study design Duration of follow-up Total number of participants Inclusion criteria Exclusion criteria Mean age (SD) Time of application of the intervention Method for calculating blood loss Diseases or health problems Abdel-Fatah 2021 [ 13 ] Egypt Randomized-controlled trial Not reported 78 Pregnancy duration was between 35 and 42 weeks of gestation. Elective cesarean delivery. Women at risk of PPH. Parity equal to or greater than 4. Multiple pregnancies. Uterine fibroids. Previous postpartum hemorrhage. History of antepartum hemorrhage in the current pregnancy or previous pregnancies. Anemia. Fetal macrosomia. Polyhydramnios. Severe medical and surgical complications involving the heart, liver, or kidney, brain disease, and blood disorders. Bleeding tendency. Hypersensitivity to TXA. History of thromboembolic disorders Tranexamic group = 28.62 (6) Control group = 27.38 (7.1) p-value 0.411 10 minutes before skin incision Not reported Risk factors for PPH as multiple pregnancies, multiparous, previous PPH, history of antepartum hemorrhage in the current or previous pregnancy, Anemia, fetal macrosomia, and polyhydramnios without a medical history of any chronic disease Abdel-Fatah 2022 [ 14 ] Egypt Randomized-controlled clinical trial 24 hours 78 Delivery between 35 and 42 weeks of gestation by elective C-section. Risk of postpartum hemorrhage. Parity equal to or greater than 4. Uterine fibroids. Previous postpartum hemorrhage. Anemia with hemoglobin < 10.5 g/dl. Fetal macrosomia. Polyhydramnios Serious complications affecting the heart, liver, or kidneys, brain diseases, and blood disorders. Tendency to bleed. Hypersensitivity to TXA. History of thromboembolic disorders Tranexamic group = 28.62 (6) Control group = 27.38 (7.1) p-value 0.411 10 minutes before skin incision Not reported Fetal macrosomia, Anemia, Twin pregnancy, Polyhydramnios, Multiparous Bhagat 2024 [ 15 ] India Double-blind randomized controlled trial. 48 hours 200 Gestation age between > 37 weeks and 18 years and 9 gm% in the recent third trimester, reports, Subject receiving spinal anesthesia for C-section, Women with high-risk pregnancies Subjects with medical conditions such as kidney, heart, or liver disease that complicate pregnancy, known cases of coagulation disorders, intrauterine fetal death, undergoing anticoagulant treatment during the week before delivery, history of seizures, allergy to TXA, or undergoing general anesthesia for a C-section The majority of patients in both groups were aged 21–25 years, followed by those aged 26–30 years, with no significant difference between the groups (p = 0.81). 20 minutes before skin incision Gravimetric method Pregnancy-induced hypertension (PIH), polyhydramnios, oligohydramnios, fetal distress, chorioamnionitis, history of C-section or PPH, twin pregnancy, prolonged and obstructed labor, prolonged induction, antepartum haemorrhage (APH) Chaiyakarn 2023 [ 16 ] Thailand Randomized double blind control trial 24 hours 60 Women diagnosed with placenta previa by transabdominal or transvaginal ultrasound at 28 weeks or more of gestation, and cases undergoing C-section for placenta previa, either by elective C-section at 37 weeks or by emergency C-section due to placenta previa Patients who show any signs of placental adhesion on the ultrasound scan prior to the procedure, patients with liver, heart, or kidney disease, patients with TXA allergy, and patients with risk factors for venous thromboembolism, such as thrombophilic disease, hematological cancer, immobilization, or morbid obesity with a BMI greater than 40 Tranexamic group = 34.7 (4.5) Control group = 32.7 (5.0) p-value 0.115 10 minutes before the skin incision Gravimetric method Placenta previa Ifunanya 2019 [ 17 ] Nigeria Randomized double blind control trial 6 weeks 168 Pregnant women who had at least one risk factor for PPH and who were to undergo elective or emergency cesarean delivery were eligible for inclusion in the study after obtaining informed consent History of cardiac, renal, and liver diseases, bleeding disorders, history of any thrombogenic episodes, anticoagulant use, and known allergy to TXA Tranexamic group = 28.2 (5.2) Control group = 28.6 (5.4) p-value 0.51 10 minutes before skin incision Nadler formula At least one of: hypertensive disorders in pregnancy, augmentation of labour, failed induction of labour, chorioamnionitis, placenta praevia, abruptio placentae, polyhydramnios, multiparity, previous PPH, coexisting fibroids, fetal macrosomia, obstructed labour, multiple gestation, and previous C-section Jawad Iqbal 2022 [ 18 ] Pakistan Double-blind, randomized, placebo-controlled trial 6 weeks 60 Women with a scheduled elective C-section who were past 38 weeks of gestation and had at least one of the following risk factors: pregnancies > 4, failed induction, obstructed or accelerated labor, placenta previa, chorioamnionitis, polyhydramnios, coexisting fibroids, fetal macrosomia, pregnancy-related hypertensive disorders, and history of C-section or PPH Women with other coexisting comorbidities such as cardiac, liver, and renal disorders, bleeding disease with a history of anticoagulant use, and allergic reaction to TXA Tranexamic group = 27.6 (4.3) Control group = 27.9 (4.7) p-value 0.61 Before skin incision Nadler formula Multiple gestations, failed induction, obstructed or augmentation of labor, placenta praevia, chorioamnionitis, polyhydroamnious, coexisting fibroids, fetal macrosomia, pregnancy-related hypertensive disorders, and a history of C-section or PPH. Mohamed 2024 [ 19 ] Algeria Double-blind, randomized controlled trial 6 weeks 800 Aged between 18 and 50 years, with a live fetus and a gestational age greater than 35 weeks, presenting one or more risk factors for PPH, such as: Age greater than 34 years, obesity, history of PPH or C-section, anemia, multiparity, uterine fibroid, preeclampsia, multifetal pregnancy, polyhydramnios, placenta previa, chorioamnionitis, macrosomia Presence of renal failure, history of venous or arterial thrombosis, epilepsy, known allergy to TXA, gestational age less than 35 weeks, fetal death, placental insertion anomaly of the accreta type Tranexamic group = 34.2 (5.5) Control group = 33.6 (5.7) p-value 0.13 15 minutes before skin incision Gravimetric method Obesity, history of PPH, or C-section, anemia, multiparity, uterine fibroid, preeclampsia, multifetal pregnancy, polyhydramnios, placenta previa, chorioamniotitis, macrosomia Nid Wongjariyakul 2025 [ 20 ] Thailand Double-blind, randomized, placebo-controlled trial 24 hours 50 Pregnant women over the age of 18, at 34 weeks or more of gestation, with a scheduled C-section and undergoing spinal anesthesia. In addition, they had to have one or more risk factors for PPH Women who had substantial medical conditions affecting the heart, liver, or kidneys, brain disorders, blood disorders, a known sensitivity to TXA, a history of or present venous or arterial thromboembolism, intrauterine fetal death, or major fetal anomalies Study group 28.9 (5.0) Control group 29.9(5.2) p-value 0.479 10–15 minutes before skin incision Gravimetric method Previous cesarean delivery, fetal macrosomia, multiple gestation, low-lying placenta, polyhydramnios placenta previa, prenatal anemia Ortuanya 2024 [ 21 ] Nigeria Double-blind randomized controlled trial. 48 hours 200 High-risk pregnant women with a previous history of PPH, co-existing uterine fibroid, multiple pregnancy, previous C-section, fetal macrosomia, placenta previa, multiple gestation, severe preeclampsia, eclampsia, and polyhydramnios Participants who had uterine rupture, intrauterine fetal death, history of bleeding disorders, history of thromboembolism, significant antepartum hemorrhage, and known allergy to tranexamic acid, and unbooked patients with prolonged obstructed labor Study group 31.8 (4.0) Control group 32.0(4.7) p-value 0.09 10 min before surgery EBL formula Placenta previa, preeclampsia, eclampsia, fetal macrosomia, polyhydramnios, twin gestation with T1 breech, preterm premature rupture of membranes (PPROM), compound presentation, transverse, one or two previous C-sections Shalaby 2022 [ 22 ] Egypt A double blind randomized controlled trial 4 weeks 160 Women with elective C-section, aged between 20 and 40 years, and with a gestational age between 37 and 41 weeks. They had one or more risk factors for increased intraoperative blood loss. In addition, women with an overstretched uterus (e.g., multiple gestation, macrosomic fetus, or polyhydramnios), placenta previa, anemia, and those who had received an intraoperative blood transfusion during a previous C-section Women with a history of thromboembolic events, allergy to TXA, and those with a morbidly adherent placenta. Women who were expected to experience intraoperative complications, such as visceral injuries Tranexamic group = 28.9 (4.46) Control group = 28.5 (4.45) p-value 0.758 15 min before surgery EBL formula and gravimetric method Anemia, polyhydramnios, fetal macrosomia, twin pregnancy, placenta previa, and received blood transfusion dur‑ ing previous C-section Risk of bias assessment Three studies with some concerns of bias were identified in the domain of deviations from intended interventions, measurement of the outcome, and selection of reported results (Fig. 2). Three studies were judged to have some concerns of bias in the domains of deviations from intended interventions, measurement of outcomes, and selection of reported results (Fig. 2). Figure 2. Risk of bias assessment Primary outcomes The evidence suggests that TXA results in a substantial reduction in total blood loss in high-risk pregnant women undergoing C-section (SMD = -1.74; 95% CI -3.09 to -0.39; I² 96.2%; p < 0.01, n = 6; 866 participants; certainty of evidence (CoE) low) (Fig. 3A). A subgroup analysis of blood loss was performed on the basis of the timing of drug administration. The studies were grouped into groups according to the administration time up to 10 minutes before the incision was made and 15–20 minutes before. The up to 10-minute group showed heterogeneity, whereas the 15–20-minute group showed no heterogeneity (0%; p = 0.51), suggesting that differences between studies mainly arose from those in which the drug was administered closer to the skin incision time. When the subgroup results were evaluated, studies that administered the drug within ten minutes of skin incision revealed a large reduction in total blood loss (SMD = -2.31; 95% CI -3.50 to -1.13; I² 94.7%; n = 4; 506 participants; CoE low). In contrast, studies in which TXA was administered 15–20 minutes before C-section likely reported reduced total blood loss with a higher level of evidence and no heterogeneity (SMD = -0.61; 95% CI -0.82 to -0.39; I² 0; n = 2; 360 participants; CoE moderate) (Supplementary data). Moreover, TXA resulted in a large reduction in intraoperative blood loss (SMD = -0.99; 95% CI -1.15 to -0.82; I² 10.2%; p = 0.34; n = 4; 988 participants; CoE high) (Fig. 3B). In addition, it probably reduces blood loss at two hours (SMD = -0.78; 95% CI -1.21 to -0.35; I² 86.5%; p = 0.00; n = 2; 1000 participants; CoE moderate) (Fig. 3C). Finally, it also led to a large reduction in blood loss greater than 1000 mL in high-risk pregnant women undergoing C-section (RR = 0.24; 95% CI 0.14 to 0.41; I² 0.0%; p = 0.47; n = 6; 1338 participants; CoE high) (Fig. 3D). Figure 3. Meta-analysis of blood loss, including total blood loss (A), intraoperative blood loss (B), blood loss at 2 hours post-partum (C), and blood loss at 24 hours post-partum (D). Secondary outcomes TXA likely reduces the risk of decreased hemoglobin values 48 hours after C-section (SMD = 1.39; 95% CI 0.58 to 2.20; I² 96.6%; p = 0.00; n = 7; 1668 participants; CoE moderate) (Fig. 4A). Similarly, when evaluating postintervention hematocrit, it was determined that TXA likely reduces the risk of decreased hematocrit 48 hours after C-section (SMD = 0.67; 95% CI: 0.48 to 0.85; I2% = 0.0%; p = 0.57; n = 4; 498 participants; CoE moderate) (Fig. 4B). In contrast, TXA had no significant effect on hospital stay (SMD = 0.03; 95% CI -0.20 to 0.25; I² = 20.4%; n = 3; 910 participants; CoE very low) (Supplementary data). When evaluating the additional use of uterotonics in women with risk factors, it was determined that TXA likely results in a large reduction in the need for additional uterotonics (RR = 0.37; 95% CI 0.24 to 0.58; I² = 49.7%; p = 0.06, n = 7; 1498 participants; CoE moderate) (Fig. 4C). The evidence suggests that TXA leads to a large reduction in the need for blood transfusions in women with high-risk pregnancies undergoing C-section (RR = 0.30; 95% CI 0.22 to 0.40; I² = 0.0%; n = 8; 1698 participants; CoE low) (Fig. 4D). Finally, for surgical intervention for postpartum hemorrhage, TXA likely slightly reduces the need for additional surgical intervention (RR = 0.35; 95% CI 0.16 to 0.78; I² = 0.0%; p = 0.35; n = 2; 260 participants; CoE moderate) (Supplementary data). With respect to safety outcomes, the meta-analysis revealed that TXA may have little or no effect on the occurrence of side effects, although the evidence is very uncertain (RR = 3.47; 95% CI 0.65 to 18.41; I² = 91.1%; p = 0.00; n = 3; 1050 participants; CoE very low) (Supplementary data). Similarly, the certainty of the evidence was also very low in relation to the occurrence of serious adverse events associated with the use of TXA (RR = 1.00; 95% CI 0.29 to 3.43; I² = 0.0%; p = 1.00; n = 3; 1060 participants) (Supplementary data). Figure 4. Meta-analyses of (A) hemoglobin values 48 hours after cesarean section, (B) hematocrit values 48 hours after cesarean section, (C) need for additional uterotonics, and (D) need for blood transfusions. Discussion The efficacy and safety of TXA versus placebo for the prevention of PPH in high-risk C-sections were evaluated. Prophylactic TXA use has consistently been shown to be associated with a significant reduction in PPH. The high-risk population allowed for the evaluation of TXA effectiveness, demonstrated efficacy in a wide range of high-risk situations,[ 23 ] and expanded the current evidence on the prophylactic use of TXA in high-risk C-sections.[ 3 , 24 ] The demonstrated effectiveness suggests that the benefits of TXA persist even in the presence of pathophysiological alterations that could interfere with its mechanism of action.[ 25 ] However, the efficacy observed in high-risk populations contrasts with the heterogeneous evidence from other pharmacological strategies to prevent PPH.[ 26 , 27 ] Unlike the WOMAN-2 study, which evaluated TXA as a treatment for established PPH,[ 28 ] this research focused on its prophylactic use. It acts before the activation of compensatory mechanisms and hyperfibrinolysis, preventing blood loss and stabilizing clots from the early stages. In contrast, its administration once bleeding has already begun inhibits only active fibrinolysis without stopping the initial hemorrhagic cascade.[ 29 ] Current recommendations for the management of PPH state that the use of TXA should be considered when initial therapies fail to control bleeding,[ 30 ] that TXA should be administered within three hours of delivery immediately after bleeding begins,[ 31 ] or that its use should be part of the initial management of established PPH, alongside uterotonics and mechanical measures.[ 30 ] However, the evidence suggests reconsidering these guidelines to include prophylactic use in high-risk populations and to standardize the timing and dosage, as 1 g intravenously is sufficient to inhibit fibrinolysis, whereas 0.5 g does not produce a significant effect.[ 32 ] Compared with the placebo, the use of TXA was associated with a reduction in total blood loss. However, heterogeneity was considerable and explained by the timing of drug administration. Subgroup analysis revealed that the administration of TXA between 10 and 20 minutes before the skin incision was associated with a significant reduction in blood loss, with less heterogeneity. This timing allows for more homogeneous and optimal plasma concentrations during the postpartum fibrinolytic activation period,[ 9 ] which is activated during the peripartum period.[ 25 ] However, the optimal time of administration remains a topic of research, and further studies on the pharmacokinetics and pharmacodynamics in relation to the effect on bleeding are needed. Evaluations of bleeding during the first two hours after C-section showed that TXA was effective, significantly reducing blood loss in the hours following the procedure.[ 33 ] Yang et al. , (2023) also reported a significant reduction in bleeding two hours after C-section, the peak effect of TXA (with a half-life of approximately three hours),[ 33 ] during which time women at risk remain susceptible to secondary bleeding.[ 9 , 34 , 35 ] The amount of perioperative blood loss also significantly differed in favor of TXA. This effect is probably due to the antifibrinolytic action of TXA during the critical hours of the perioperative period.[ 33 ] Similar findings have been reported, showing that the use of a drug is associated with a reduction in the need for transfusions and the risk of severe bleeding.[ 36 – 40 ] In relation to blood loss exceeding 1000 mL, TXA was associated with a significant reduction in bleeding, significantly reducing the need for surgical interventions, from conservative techniques such as uterine packing to more invasive procedures such as arterial embolization, hemostatic ligatures, and postpartum hysterectomy.[ 21 , 41 ] It significantly reduces the need for transfusions, demonstrating its effectiveness in controlling bleeding, supported by better maintenance of hematocrit and hemoglobin postsurgery in favor of the drug,[ 13 , 15 , 21 , 41 ] reducing the costs associated with transfusions and decreasing the risks inherent in the procedure.[ 42 ] These findings are consistent with results reported by other authors, who support its use as a prophylactic intervention to prevent severe PPH, especially in high-risk women,[ 43 ] and the need for additional interventions such as complementary uterotonics, surgery, and blood transfusions.[ 36 – 40 ] A lower need for complementary uterotonics was observed, and TXA can effectively complement these strategies through its mechanism of action, allowing for a synergistic effect in the management and prevention of PPH.[ 41 ] The safety assessment revealed no significant differences in the frequency of side effects between TXA and the placebo. Mild events were generally self-limiting and manageable in the perioperative setting, and no differences were observed between groups regarding serious events, which is consistent with previous findings and supports the safety profile of TXA for obstetric prophylaxis.[ 42 , 44 ] Evidence indicates that TXA is safe during pregnancy and lactation. A meta-analysis of more than 19,000 participants revealed no significant adverse effects in newborns, and drug levels in breast milk accounted for only 1% of maternal serum levels. There were no differences in long-term outcomes, including neurological development, general health, and infant mortality. Occasional complications, such as low birth weight or preterm delivery, are related to maternal conditions rather than the drug. Therefore, breastfeeding is considered safe, and the U.S. Food and Drug Administration classifies TXA as category B during pregnancy.[ 45 ] The main limitation of this study is its lack of representativeness, since most studies are from specific regions, making it difficult to generalize the results to different clinical contexts. However, the greatest strength of the study is its contribution to the available evidence through specific research in high-risk women, where the clinical, pathophysiological, and risk factors influencing PPH were examined in detail. Research on TXA in obstetrics is needed to optimize its efficacy and safety, determine the optimal dose, evaluate different regimens and routes of administration, and compare prophylactic and therapeutic approaches. Multicenter trials that stratify patients by risk factors are also needed to evaluate effectiveness in different subgroups. Research is also needed on long-term safety, effects on breastfeeding, and the development of predictive biomarkers. Similarly, the integration of artificial intelligence models is necessary to enable personalized PPH prevention, optimize treatment efficacy, and reduce associated risks and costs. Conclusion TXA, as a prophylactic intervention, has consistent and clinically significant benefits in reducing blood loss in high-risk C-sections. This can result in a large reduction in total blood loss in patients undergoing C-section and probably reduces blood loss between 15 and 20 minutes before skin incision, with a more homogeneous effect and a significant reduction in heterogeneity between studies. An early reduction in blood loss is likely to result in a large decrease at two hours post-operatively, as well as a large reduction in intraoperative loss and in cases with hemorrhage greater than 1000 mL. In terms of hematological parameters, TXA probably reduces the postoperative decrease in hemoglobin and results in a reduced risk of a decrease in hematocrit, which reinforces the effectiveness of PPH prevention. It also probably results in a large reduction in the additional use of uterotonics and the need for blood transfusions and may reduce the need for complementary surgical interventions to control bleeding. Abbreviations PPH: Postpartum hemorrhage C-section: Cesarean section TXA: Tranexamic acid MD: Mean difference SMD: Standardized mean difference CI: Confidence interval RR: Relative risk EBL: Estimated blood loss CoE: Certainty of evidence Declarations Ethics approval and consent to participate Not applicable Consent for publication All authors consent to the publication of the manuscript. Availability of data and materials No datasets were generated or analyzed during the current study. Competing interests The authors declare that they have no competing interests. Funding This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors. Authors' contributions Conceptualization: X.S.L., and D.A.T.; Methodology: D.A.T.; Software: D.A.T.; Validation: X.S.L., H.C.G., and D.A.T.; Formal analysis: H.C.G., C.M.G., and D.A.T.; Investigation: X.S.L., H.C.G., C.M.G., K.V.A., Z.I.A., and D.A.T.; Resources: D.A.T.; Data curation: D.A.T.; Writing original draft: H.C.G., C.M.G., and D.A.T.; Writing review and editing: X.S.L., H.C.G., C.M.G., K.V.A., Z.I.A., and D.A.T.; Visualization: H.C.G., D.A.T.; Supervision: D.A.T.; Project administration: D.A.T. Acknowledgments We thank Dr. Josué Ramos and Jorge Llanes, M.A for reviewing the translation and grammar of the manuscript. Authors' information National Institute of Health, San Salvador, El Salvador Xochitl Sandoval López, Hazel C. García, Cesar M. Gavidia, Karina V. Alam, Zaida I. Álvarez, and David A. Tejada Corresponding author: David A. 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The Lancet. 2024; 404(10463):p 1657–1667. https://doi.org/10.1016/S0140-6736(24)02102-0 Guinness F, Hanley C, Spring A. Meta-analysis: the prophylactic use of tranexamic acid to reduce blood loss during caesarean delivery. Ir. J. Med. Sci . 2024; 194:p 311–322. https://doi.org/10.1007/s11845-024-03834-y Tranexamic Acid, in: Drugs Lact. Database Lact. National Institute of Child Health and Human Development, Bethesda (MD), 2006. Accessed August 27, 2025. Available at: http://www.ncbi.nlm.nih.gov/books/NBK501734/ Additional Declarations The authors declare no competing interests. Supplementary Files Supplementarymaterial.docx Supplementary material Cite Share Download PDF Status: Posted Version 1 posted You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. 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2","display":"","copyAsset":false,"role":"figure","size":870731,"visible":true,"origin":"","legend":"\u003cp\u003eRisk of bias assessment\u003c/p\u003e","description":"","filename":"Figure2.png","url":"https://assets-eu.researchsquare.com/files/rs-7961244/v1/eff10a35a82bcf3faca95758.png"},{"id":94633800,"identity":"0b3fbb94-13c0-4eda-abff-8e79c099ada9","added_by":"auto","created_at":"2025-10-29 06:39:16","extension":"png","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":2982018,"visible":true,"origin":"","legend":"\u003cp\u003eMeta-analysis of blood loss, including total blood loss (A), intraoperative blood loss (B), blood loss at 2 hours post-partum (C), and blood loss at 24 hours post-partum (D).\u003c/p\u003e","description":"","filename":"Figure3.png","url":"https://assets-eu.researchsquare.com/files/rs-7961244/v1/2761e04bf20c27f9f4d0b9a2.png"},{"id":94633799,"identity":"a1a4866d-57eb-4fff-a803-6ecf7ed92acf","added_by":"auto","created_at":"2025-10-29 06:39:16","extension":"png","order_by":4,"title":"Figure 4","display":"","copyAsset":false,"role":"figure","size":3175150,"visible":true,"origin":"","legend":"\u003cp\u003eMeta-analyses of (A) hemoglobin values 48 hours after cesarean section, (B) hematocrit values 48 hours after cesarean section, (C) need for additional uterotonics, and (D) need for blood transfusions.\u003c/p\u003e","description":"","filename":"Figure4.png","url":"https://assets-eu.researchsquare.com/files/rs-7961244/v1/48922b8a9fb72331c1ee65eb.png"},{"id":94672138,"identity":"e2a03aee-3efa-4f06-aef2-b88243fc57e4","added_by":"auto","created_at":"2025-10-29 13:39:20","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":7651244,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-7961244/v1/7c540291-50fe-49b1-81e8-8c9b58289de7.pdf"},{"id":94633792,"identity":"f859e19d-e4bf-4c7c-b1a3-d9f70dd6840d","added_by":"auto","created_at":"2025-10-29 06:39:16","extension":"docx","order_by":1,"title":"","display":"","copyAsset":false,"role":"supplement","size":362906,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eSupplementary material\u003c/strong\u003e\u003c/p\u003e","description":"","filename":"Supplementarymaterial.docx","url":"https://assets-eu.researchsquare.com/files/rs-7961244/v1/412405a94284e148cce26c8d.docx"}],"financialInterests":"The authors declare no competing interests.","formattedTitle":"\u003cp\u003e\u003cstrong\u003eProphylactic use of tranexamic acid to prevent postpartum hemorrhage in high-risk cesarean deliveries: a systematic review and meta-analysis\u003c/strong\u003e\u003c/p\u003e","fulltext":[{"header":"Background","content":"\u003cp\u003ePostpartum hemorrhage (PPH) is one of the leading causes of maternal morbidity and mortality worldwide and is particularly relevant in women who have undergone cesarean section (C-section).[\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e] This type of hemorrhage is defined as blood loss exceeding 1000 mL after delivery or accompanied by symptoms or signs of hypovolemia within 24 hours after birth,[\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e] which can lead to serious complications or death.[\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e] Despite medical advances, the PPH continues to be a challenge in obstetrics, with direct implications for maternal health and healthcare costs.[\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e]\u003c/p\u003e\u003cp\u003eGlobally, the proportion of cesarean deliveries is increasing,[\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e] accounting for approximately 30% of deliveries in developed countries and 20% of all deliveries worldwide.[\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e] It is estimated that between 1% and 5% of these procedures may be complicated by PPH.[\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e] Maternal mortality attributed to PPH remains high in some regions,[\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e] with the prevalence varying by region, ranging from 2.4% to 12.1%.[\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e]\u003c/p\u003e\u003cp\u003eWomen considered at high risk are more likely to suffer from PPH due to factors such as a history of hemorrhage, multiple pregnancies, placenta previa, or placental abruption, among others.\u003c/p\u003e\u003cp\u003eIn this context, tranexamic acid (TXA) has emerged as an essential option for reducing PPH in women undergoing C-section.[\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e] TXA is an antifibrinolytic agent that can help control excessive blood loss.[\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e] Its use has become widespread in various surgical and trauma settings, and it has been proposed as a prophylactic intervention for PPH.[\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e] However, evidence of its efficacy compared with that of placebo or standard treatment remains under investigation.[\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e]\u003c/p\u003e\u003cp\u003eTherefore, this systematic review aims to evaluate the efficacy and safety of TXA for the prevention of PPH in women undergoing C-section and compare its use with that of placebo or standard treatment.\u003c/p\u003e"},{"header":"Methods","content":"\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e\u003ch2\u003eStudy design\u003c/h2\u003e\u003cp\u003e A systematic review with meta-analysis was conducted following the recommendations of the PRISMA 2020 statement. This protocol has been registered in the PROSPERO database with the registration number 2025 CRD420251087054. Available at: \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://www.crd.york.ac.uk/PROSPERO/view/CRD420251087054\u003c/span\u003e\u003cspan address=\"https://www.crd.york.ac.uk/PROSPERO/view/CRD420251087054\" targettype=\"URL\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/p\u003e\u003c/div\u003e\n\u003ch3\u003eSearches\u003c/h3\u003e\n\u003cp\u003eA systematic search was conducted in the PubMed, Scopus, Web of Science, EMBASE, CINAHL, Cochrane Library, ClinicalTrials.gov, and International Clinical Trials Registry Platforms of the World Health Organization databases from their inception to July 3, 2025. For each database, a tailored search strategy was applied, using free-text terms in all cases, the Medical Subject Headings thesaurus in PubMed, and the Emtree thesaurus in EMBASE and Scopus. The main search terms included \"postpartum hemorrhage\", \"tranexamic acid\", \"cesarean section\", and \"high-risk pregnancy\". No language or publication date restrictions were applied.\u003c/p\u003e\n\u003ch3\u003eEligibility criteria\u003c/h3\u003e\n\u003cp\u003eAll randomized controlled trials that evaluated pregnant women and compared TXA prophylaxis with placebo or standard treatment were included. Studies included women aged 18 years or older with medical or obstetric conditions associated with a high risk of hemorrhage. Studies involving women with hypersensitivity to TXA, hematological disorders with a predisposition to bleeding, a history of thromboembolism, or ongoing anticoagulant treatment were excluded.\u003c/p\u003e\n\u003ch3\u003eOutcomes\u003c/h3\u003e\n\u003cp\u003eThe primary outcomes were total blood loss, defined as the estimated volume of blood loss at the end of the study; total blood loss at two hours, which corresponds to the volume lost during delivery and the two hours following delivery; and the incidence of postpartum hemorrhage, defined as a loss of more than 1000 mL or the need for red blood cell transfusion within two days after delivery.\u003c/p\u003e\u003cp\u003eThe secondary outcomes included changes in hemoglobin and hematocrit; clinical and laboratory variables related to blood loss; adverse events; the length of hospital stay; the need for blood transfusion; and additional uterotonics, which were systematically documented.\u003c/p\u003e\n\u003ch3\u003eSelection process\u003c/h3\u003e\n\u003cp\u003eThe records obtained from the electronic searches were exported to EndNote, where they were consolidated into a library, and duplicates were removed. The library was then uploaded to Rayyan for initial screening by title and abstract. Studies selected in the initial screening were evaluated in full text for a new review process. Eligible studies were included in the review, and the data extraction process was performed. This stage was assessed blindly and independently by the reviewers. Conflicts were resolved at each stage by team consensus.\u003c/p\u003e\u003cdiv id=\"Sec8\" class=\"Section2\"\u003e\u003ch2\u003eData extraction\u003c/h2\u003e\u003cp\u003eData from each study were extracted individually via a predesigned format in a Microsoft Excel spreadsheet. For each analysis, information was collected on the author, year of publication, country, type of study, number of participants per intervention group, mean age per group, eligibility criteria, and description of the intervention and control, as well as primary and secondary outcomes.\u003c/p\u003e\u003c/div\u003e\n\u003ch3\u003eAssessment of risk of bias\u003c/h3\u003e\n\u003cp\u003eThe risk of bias was assessed via the RoB 2.0 tool by the reviewers. RoB was classified by domain as low, with some concerns, or high. Disagreements were resolved through discussion with a sixth reviewer (XSL).\u003c/p\u003e\n\u003ch3\u003eData synthesis\u003c/h3\u003e\n\u003cp\u003eThe meta-analysis was performed via a random effects model, and the inverse variance method was used to estimate the effects of TXA compared with those of the placebo. The variance between studies (tau\u0026sup2;) was estimated via the Paule‒Mandel method.\u003c/p\u003e\u003cp\u003eContinuous outcomes were analyzed via mean differences (MDs) or standardized mean differences (SMDs), as appropriate, accompanied by 95% confidence intervals (95% CIs).\u003c/p\u003e\u003cp\u003eFor dichotomous outcomes, the effect was quantified using the relative risk (RR) with 95% CI. In studies with no events in one or both groups, a continuity correction was applied. The confidence intervals were adjusted via the Hartung‒Knapp‒Sidik‒Jonkman method for meta-analyses with more than five studies or the profile likelihood method for those with five or fewer studies.\u003c/p\u003e\u003cp\u003eHeterogeneity between studies was assessed via the I\u0026sup2; statistic, considering low (\u0026lt;\u0026thinsp;30%), moderate (30\u0026ndash;60%), and high (\u0026gt;\u0026thinsp;60%) levels. Heterogeneity was explored via subgroup analysis. For sensitivity analysis, meta-analyses were performed, excluding studies with high heterogeneity or with specific characteristics that could influence the results. The analysis was performed in R v4.4.2 via the metabin function of the meta package.\u003c/p\u003e\u003cdiv id=\"Sec11\" class=\"Section2\"\u003e\u003ch2\u003eGRADE assessment\u003c/h2\u003e\u003cp\u003eThe certainty of the evidence and the level of recommendation were assessed via the GRADE methodology, which considers the domains of risk of bias, inconsistency, indirect evidence, imprecision, and publication bias. The assessment was performed for each outcome and summarized in summary of evidence (SoE) tables, developed via the online software GRADEpro GDT.\u003c/p\u003e\u003c/div\u003e"},{"header":"Results","content":"\u003cp\u003eA total of 1811 articles were identified in five databases, of which 1006 duplicates were removed. After duplicate removal, 805 articles were screened by title and abstract, and 740 were excluded because they did not meet the inclusion criteria. Sixty-five full-text articles were analyzed, and 55 were discarded because of an incorrect study design (n\u0026thinsp;=\u0026thinsp;16), an incorrect population (n\u0026thinsp;=\u0026thinsp;6), an unavailable full-text paper (n\u0026thinsp;=\u0026thinsp;4), unpublished results (n\u0026thinsp;=\u0026thinsp;13), an incorrect publication type (n\u0026thinsp;=\u0026thinsp;14), or an incorrect outcome (n\u0026thinsp;=\u0026thinsp;2). Finally, 10 randomized clinical trials (n\u0026thinsp;=\u0026thinsp;1854) were included for qualitative and quantitative analyses.[\u003cspan additionalcitationids=\"CR14 CR15 CR16 CR17 CR18 CR19 CR20 CR21\" citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e] (Fig.\u0026nbsp;1).\u003c/p\u003e\u003cp\u003e\u003cb\u003eFigure 1.\u003c/b\u003e PRISMA 2020 flow chart.\u003c/p\u003e\u003cdiv id=\"Sec13\" class=\"Section2\"\u003e\u003ch2\u003eCharacteristics of participants and included studies\u003c/h2\u003e\u003cp\u003eTen randomized clinical trials were published between 2019 and 2025 and were conducted in some regions of the world, including Asia and Africa. The number of participants in the studies ranged from 50\u0026ndash;200 women. No significant differences were observed in the mean age between groups within studies or when comparisons were made among studies (p\u0026thinsp;\u0026lt;\u0026thinsp;0.05).\u003c/p\u003e\u003cp\u003eBlood loss was estimated via the weighing of surgical drapes and towels (gravimetric method) and two formula-based calculations: estimated blood loss (EBL) and the Nadler formula. The follow-up period was 24 to 48 hours in most studies, with some studies extending to four or six weeks (Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e).\u003c/p\u003e\u003cp\u003e\u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab1\" border=\"1\"\u003e\u003ccaption language=\"En\"\u003e\u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e\u003cdiv class=\"CaptionContent\"\u003e\u003cp\u003eCharacteristics of the included studies\u003c/p\u003e\u003c/div\u003e\u003c/caption\u003e\u003ccolgroup cols=\"11\"\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e\u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c7\" colnum=\"7\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c8\" colnum=\"8\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c9\" colnum=\"9\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c10\" colnum=\"10\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c11\" colnum=\"11\"\u003e\u003c/div\u003e\u003cthead\u003e\u003ctr\u003e\u003cth align=\"left\" colname=\"c1\"\u003e\u003cp\u003eAuthor\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c2\"\u003e\u003cp\u003eCountry/Region\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c3\"\u003e\u003cp\u003eStudy design\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c4\"\u003e\u003cp\u003eDuration of follow-up\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c5\"\u003e\u003cp\u003eTotal number of participants\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c6\"\u003e\u003cp\u003eInclusion criteria\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c7\"\u003e\u003cp\u003eExclusion criteria\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c8\"\u003e\u003cp\u003eMean age (SD)\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c9\"\u003e\u003cp\u003eTime of application of the intervention\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c10\"\u003e\u003cp\u003eMethod for calculating blood loss\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c11\"\u003e\u003cp\u003eDiseases or health problems\u003c/p\u003e\u003c/th\u003e\u003c/tr\u003e\u003c/thead\u003e\u003ctbody\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eAbdel-Fatah 2021 [\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e]\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eEgypt\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003eRandomized-controlled trial\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003eNot reported\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e78\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003ePregnancy duration was between 35 and 42 weeks of gestation. Elective cesarean delivery. Women at risk of PPH. Parity equal to or greater than 4. Multiple pregnancies. Uterine fibroids. Previous postpartum hemorrhage. History of antepartum hemorrhage in the current pregnancy or previous pregnancies. Anemia. Fetal macrosomia. Polyhydramnios.\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003eSevere medical and surgical complications involving the heart, liver, or kidney, brain disease, and blood disorders. Bleeding tendency. Hypersensitivity to TXA. History of thromboembolic disorders\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003eTranexamic group\u0026thinsp;=\u0026thinsp;28.62 (6)\u003c/p\u003e\u003cp\u003eControl group\u0026thinsp;=\u0026thinsp;27.38 (7.1)\u003c/p\u003e\u003cp\u003ep-value 0.411\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u003cp\u003e10 minutes before skin incision\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c10\"\u003e\u003cp\u003eNot reported\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c11\"\u003e\u003cp\u003eRisk factors for PPH as multiple pregnancies, multiparous, previous PPH, history of antepartum hemorrhage in the current or previous pregnancy, Anemia, fetal macrosomia, and polyhydramnios without a medical history of any chronic disease\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eAbdel-Fatah 2022 [\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e]\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eEgypt\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003eRandomized-controlled\u003c/p\u003e\u003cp\u003eclinical trial\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e24 hours\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e78\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003eDelivery between 35 and 42 weeks of gestation by elective C-section. Risk of postpartum hemorrhage. Parity equal to or greater than 4. Uterine fibroids. Previous postpartum hemorrhage. Anemia with hemoglobin\u0026thinsp;\u0026lt;\u0026thinsp;10.5 g/dl. Fetal macrosomia. Polyhydramnios\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003eSerious complications affecting the heart, liver, or kidneys, brain diseases, and blood disorders. Tendency to bleed. Hypersensitivity to TXA. History of thromboembolic disorders\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003eTranexamic group\u0026thinsp;=\u0026thinsp;28.62 (6)\u003c/p\u003e\u003cp\u003eControl group\u0026thinsp;=\u0026thinsp;27.38 (7.1)\u003c/p\u003e\u003cp\u003ep-value 0.411\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u003cp\u003e10 minutes before skin incision\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c10\"\u003e\u003cp\u003eNot reported\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c11\"\u003e\u003cp\u003eFetal macrosomia, Anemia, Twin\u003c/p\u003e\u003cp\u003epregnancy, Polyhydramnios, Multiparous\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eBhagat 2024 [\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e]\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eIndia\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003eDouble-blind randomized controlled trial.\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e48 hours\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e200\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003eGestation age between \u0026gt;\u0026thinsp;37 weeks and \u0026lt;\u0026thinsp;42 weeks, Age\u0026thinsp;\u0026gt;\u0026thinsp;18 years and \u0026lt;\u0026thinsp;35 years, Alive fetus, Hemoglobin\u0026thinsp;\u0026gt;\u0026thinsp;9 gm% in the recent third trimester, reports, Subject receiving spinal anesthesia for C-section, Women with high-risk pregnancies\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003eSubjects with medical conditions such as kidney, heart, or liver disease that complicate pregnancy, known cases of coagulation disorders, intrauterine fetal death, undergoing anticoagulant treatment during the week before delivery, history of seizures, allergy to TXA, or undergoing general anesthesia for a C-section\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003eThe majority of patients in both groups were aged 21\u0026ndash;25 years, followed by those aged 26\u0026ndash;30 years, with no significant difference between the groups (p\u0026thinsp;=\u0026thinsp;0.81).\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u003cp\u003e20 minutes before skin incision\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c10\"\u003e\u003cp\u003eGravimetric method\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c11\"\u003e\u003cp\u003ePregnancy-induced hypertension (PIH), polyhydramnios, oligohydramnios, fetal distress, chorioamnionitis, history of C-section or PPH, twin pregnancy, prolonged and obstructed labor, prolonged induction, antepartum haemorrhage (APH)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eChaiyakarn 2023 [\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e]\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eThailand\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003eRandomized double blind control trial\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e24 hours\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e60\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003eWomen diagnosed with placenta previa by transabdominal or transvaginal ultrasound at 28 weeks or more of gestation, and cases undergoing C-section for placenta previa, either by elective C-section at 37 weeks or by emergency C-section due to placenta previa\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003ePatients who show any signs of placental adhesion on the ultrasound scan prior to the procedure, patients with liver, heart, or kidney disease, patients with TXA allergy, and patients with risk factors for venous thromboembolism, such as thrombophilic disease, hematological cancer, immobilization, or morbid obesity with a BMI greater than 40\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003eTranexamic group\u0026thinsp;=\u0026thinsp;34.7 (4.5)\u003c/p\u003e\u003cp\u003eControl group\u0026thinsp;=\u0026thinsp;32.7 (5.0)\u003c/p\u003e\u003cp\u003ep-value 0.115\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u003cp\u003e10 minutes before the skin incision\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c10\"\u003e\u003cp\u003eGravimetric method\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c11\"\u003e\u003cp\u003ePlacenta previa\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eIfunanya 2019 [\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e]\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eNigeria\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003eRandomized double blind control trial\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e6 weeks\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e168\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003ePregnant women who had at least one risk factor for PPH and who were to undergo elective or emergency cesarean delivery were eligible for inclusion in the study after obtaining informed consent\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003eHistory of cardiac, renal, and liver diseases, bleeding disorders, history of any thrombogenic episodes, anticoagulant use, and known allergy to TXA\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003eTranexamic group\u0026thinsp;=\u0026thinsp;28.2 (5.2)\u003c/p\u003e\u003cp\u003eControl group\u0026thinsp;=\u0026thinsp;28.6 (5.4)\u003c/p\u003e\u003cp\u003ep-value 0.51\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u003cp\u003e10 minutes before skin incision\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c10\"\u003e\u003cp\u003eNadler formula\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c11\"\u003e\u003cp\u003eAt least one of: hypertensive disorders in pregnancy, augmentation of labour, failed induction of labour, chorioamnionitis, placenta praevia, abruptio placentae, polyhydramnios, multiparity, previous PPH, coexisting fibroids, fetal macrosomia, obstructed labour, multiple gestation, and previous C-section\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eJawad Iqbal 2022 [\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e]\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003ePakistan\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003eDouble-blind, randomized, placebo-controlled trial\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e6 weeks\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e60\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003eWomen with a scheduled elective C-section who were past 38 weeks of gestation and had at least one of the following risk factors: pregnancies\u0026thinsp;\u0026gt;\u0026thinsp;4, failed induction, obstructed or accelerated labor, placenta previa, chorioamnionitis, polyhydramnios, coexisting fibroids, fetal macrosomia, pregnancy-related hypertensive disorders, and history of C-section or PPH\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003eWomen with other coexisting\u003c/p\u003e\u003cp\u003ecomorbidities such as cardiac, liver, and renal\u003c/p\u003e\u003cp\u003edisorders, bleeding disease with a history of\u003c/p\u003e\u003cp\u003eanticoagulant use, and allergic reaction to TXA\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003eTranexamic group\u0026thinsp;=\u0026thinsp;27.6 (4.3)\u003c/p\u003e\u003cp\u003eControl group\u0026thinsp;=\u0026thinsp;27.9 (4.7)\u003c/p\u003e\u003cp\u003ep-value 0.61\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u003cp\u003eBefore\u003c/p\u003e\u003cp\u003eskin incision\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c10\"\u003e\u003cp\u003eNadler formula\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c11\"\u003e\u003cp\u003eMultiple gestations, failed induction,\u003c/p\u003e\u003cp\u003eobstructed or augmentation of labor, placenta\u003c/p\u003e\u003cp\u003epraevia, chorioamnionitis, polyhydroamnious,\u003c/p\u003e\u003cp\u003ecoexisting fibroids, fetal macrosomia, pregnancy-related hypertensive disorders, and a history of\u003c/p\u003e\u003cp\u003eC-section or PPH.\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eMohamed 2024 [\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e]\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eAlgeria\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003eDouble-blind, randomized controlled trial\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e6 weeks\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e800\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003eAged between 18 and 50 years, with a live fetus and a gestational age greater than 35 weeks, presenting one or more risk factors for PPH, such as: Age greater than 34 years, obesity, history of PPH or C-section, anemia, multiparity, uterine fibroid, preeclampsia, multifetal pregnancy, polyhydramnios, placenta previa, chorioamnionitis, macrosomia\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003ePresence of renal failure, history of venous or arterial thrombosis, epilepsy, known allergy to TXA, gestational age less than 35 weeks, fetal death, placental insertion anomaly of the accreta type\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003eTranexamic group\u0026thinsp;=\u0026thinsp;34.2 (5.5)\u003c/p\u003e\u003cp\u003eControl group\u0026thinsp;=\u0026thinsp;33.6 (5.7)\u003c/p\u003e\u003cp\u003ep-value 0.13\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u003cp\u003e15 minutes before skin incision\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c10\"\u003e\u003cp\u003eGravimetric method\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c11\"\u003e\u003cp\u003eObesity, history of PPH, or C-section, anemia, multiparity, uterine fibroid, preeclampsia, multifetal pregnancy, polyhydramnios, placenta previa, chorioamniotitis, macrosomia\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eNid Wongjariyakul 2025 [\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e]\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eThailand\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003eDouble-blind, randomized,\u003c/p\u003e\u003cp\u003eplacebo-controlled trial\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e24 hours\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e50\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003ePregnant women over the age of 18, at 34 weeks or more of gestation, with a scheduled C-section and undergoing spinal anesthesia. In addition, they had to have one or more risk factors for PPH\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003eWomen who had substantial medical conditions affecting the heart, liver, or kidneys, brain disorders, blood disorders, a known sensitivity to TXA, a history of or present venous or arterial thromboembolism, intrauterine fetal death, or major fetal anomalies\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003eStudy group\u003c/p\u003e\u003cp\u003e28.9 (5.0)\u003c/p\u003e\u003cp\u003eControl group\u003c/p\u003e\u003cp\u003e29.9(5.2)\u003c/p\u003e\u003cp\u003ep-value 0.479\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u003cp\u003e10\u0026ndash;15\u003c/p\u003e\u003cp\u003eminutes before skin incision\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c10\"\u003e\u003cp\u003eGravimetric method\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c11\"\u003e\u003cp\u003ePrevious cesarean delivery, fetal macrosomia, multiple gestation, low-lying placenta, polyhydramnios\u003c/p\u003e\u003cp\u003eplacenta previa, prenatal anemia\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eOrtuanya 2024 [\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e]\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eNigeria\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003eDouble-blind randomized controlled trial.\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e48 hours\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e200\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003eHigh-risk pregnant women with a previous history of PPH, co-existing uterine fibroid, multiple pregnancy, previous C-section, fetal macrosomia, placenta previa, multiple gestation, severe preeclampsia, eclampsia, and polyhydramnios\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003eParticipants who had uterine rupture, intrauterine fetal death, history of bleeding disorders, history of thromboembolism, significant antepartum hemorrhage, and known allergy to tranexamic acid, and unbooked patients with prolonged obstructed labor\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003eStudy group\u003c/p\u003e\u003cp\u003e31.8 (4.0)\u003c/p\u003e\u003cp\u003eControl group\u003c/p\u003e\u003cp\u003e32.0(4.7)\u003c/p\u003e\u003cp\u003ep-value 0.09\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u003cp\u003e10 min before surgery\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c10\"\u003e\u003cp\u003eEBL formula\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c11\"\u003e\u003cp\u003ePlacenta previa, preeclampsia, eclampsia, fetal macrosomia, polyhydramnios, twin gestation with T1 breech, preterm premature rupture of membranes (PPROM), compound presentation, transverse, one or two previous C-sections\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eShalaby 2022 [\u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e]\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eEgypt\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003eA double blind randomized controlled trial\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e4 weeks\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e160\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003eWomen with elective C-section, aged between 20 and 40 years, and with a gestational age between 37 and 41 weeks. They had one or more risk factors for increased intraoperative blood loss. In addition, women with an overstretched uterus (e.g., multiple gestation, macrosomic fetus, or polyhydramnios), placenta previa, anemia, and those who had received an intraoperative blood transfusion during a previous C-section\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003eWomen with a history of thromboembolic events, allergy to TXA, and those with a morbidly adherent placenta. Women who were expected to experience intraoperative complications, such as visceral injuries\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003eTranexamic group\u0026thinsp;=\u0026thinsp;28.9 (4.46)\u003c/p\u003e\u003cp\u003eControl group\u0026thinsp;=\u0026thinsp;28.5 (4.45)\u003c/p\u003e\u003cp\u003ep-value 0.758\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u003cp\u003e15 min before surgery\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c10\"\u003e\u003cp\u003eEBL formula and gravimetric method\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c11\"\u003e\u003cp\u003eAnemia, polyhydramnios, fetal macrosomia, twin pregnancy, placenta previa, and received blood transfusion dur‑\u003c/p\u003e\u003cp\u003eing previous C-section\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003c/tbody\u003e\u003c/colgroup\u003e\u003c/table\u003e\u003c/div\u003e\u003c/p\u003e\u003c/div\u003e\u003cdiv id=\"Sec14\" class=\"Section2\"\u003e\u003ch2\u003eRisk of bias assessment\u003c/h2\u003e\u003cp\u003eThree studies with some concerns of bias were identified in the domain of deviations from intended interventions, measurement of the outcome, and selection of reported results (Fig.\u0026nbsp;2).\u003c/p\u003e\u003cp\u003eThree studies were judged to have some concerns of bias in the domains of deviations from intended interventions, measurement of outcomes, and selection of reported results (Fig.\u0026nbsp;2).\u003c/p\u003e\u003cp\u003e\u003cb\u003eFigure 2.\u003c/b\u003e Risk of bias assessment\u003c/p\u003e\u003c/div\u003e\u003cdiv id=\"Sec15\" class=\"Section2\"\u003e\u003ch2\u003ePrimary outcomes\u003c/h2\u003e\u003cp\u003eThe evidence suggests that TXA results in a substantial reduction in total blood loss in high-risk pregnant women undergoing C-section (SMD = -1.74; 95% CI -3.09 to -0.39; I\u0026sup2; 96.2%; p\u0026thinsp;\u0026lt;\u0026thinsp;0.01, n\u0026thinsp;=\u0026thinsp;6; 866 participants; certainty of evidence (CoE) low) (Fig.\u0026nbsp;3A). A subgroup analysis of blood loss was performed on the basis of the timing of drug administration. The studies were grouped into groups according to the administration time up to 10 minutes before the incision was made and 15\u0026ndash;20 minutes before. The up to 10-minute group showed heterogeneity, whereas the 15\u0026ndash;20-minute group showed no heterogeneity (0%; p\u0026thinsp;=\u0026thinsp;0.51), suggesting that differences between studies mainly arose from those in which the drug was administered closer to the skin incision time. When the subgroup results were evaluated, studies that administered the drug within ten minutes of skin incision revealed a large reduction in total blood loss (SMD = -2.31; 95% CI -3.50 to -1.13; I\u0026sup2; 94.7%; n\u0026thinsp;=\u0026thinsp;4; 506 participants; CoE low). In contrast, studies in which TXA was administered 15\u0026ndash;20 minutes before C-section likely reported reduced total blood loss with a higher level of evidence and no heterogeneity (SMD = -0.61; 95% CI -0.82 to -0.39; I\u0026sup2; 0; n\u0026thinsp;=\u0026thinsp;2; 360 participants; CoE moderate) (Supplementary data).\u003c/p\u003e\u003cp\u003eMoreover, TXA resulted in a large reduction in intraoperative blood loss (SMD = -0.99; 95% CI -1.15 to -0.82; I\u0026sup2; 10.2%; p\u0026thinsp;=\u0026thinsp;0.34; n\u0026thinsp;=\u0026thinsp;4; 988 participants; CoE high) (Fig.\u0026nbsp;3B). In addition, it probably reduces blood loss at two hours (SMD = -0.78; 95% CI -1.21 to -0.35; I\u0026sup2; 86.5%; p\u0026thinsp;=\u0026thinsp;0.00; n\u0026thinsp;=\u0026thinsp;2; 1000 participants; CoE moderate) (Fig.\u0026nbsp;3C). Finally, it also led to a large reduction in blood loss greater than 1000 mL in high-risk pregnant women undergoing C-section (RR\u0026thinsp;=\u0026thinsp;0.24; 95% CI 0.14 to 0.41; I\u0026sup2; 0.0%; p\u0026thinsp;=\u0026thinsp;0.47; n\u0026thinsp;=\u0026thinsp;6; 1338 participants; CoE high) (Fig.\u0026nbsp;3D).\u003c/p\u003e\u003cp\u003e\u003cb\u003eFigure 3.\u003c/b\u003e Meta-analysis of blood loss, including total blood loss (A), intraoperative blood loss (B), blood loss at 2 hours post-partum (C), and blood loss at 24 hours post-partum (D).\u003c/p\u003e\u003c/div\u003e\u003cdiv id=\"Sec16\" class=\"Section2\"\u003e\u003ch2\u003eSecondary outcomes\u003c/h2\u003e\u003cp\u003eTXA likely reduces the risk of decreased hemoglobin values 48 hours after C-section (SMD\u0026thinsp;=\u0026thinsp;1.39; 95% CI 0.58 to 2.20; I\u0026sup2; 96.6%; p\u0026thinsp;=\u0026thinsp;0.00; n\u0026thinsp;=\u0026thinsp;7; 1668 participants; CoE moderate) (Fig.\u0026nbsp;4A). Similarly, when evaluating postintervention hematocrit, it was determined that TXA likely reduces the risk of decreased hematocrit 48 hours after C-section (SMD\u0026thinsp;=\u0026thinsp;0.67; 95% CI: 0.48 to 0.85; I2% = 0.0%; p\u0026thinsp;=\u0026thinsp;0.57; n\u0026thinsp;=\u0026thinsp;4; 498 participants; CoE moderate) (Fig.\u0026nbsp;4B). In contrast, TXA had no significant effect on hospital stay (SMD\u0026thinsp;=\u0026thinsp;0.03; 95% CI -0.20 to 0.25; I\u0026sup2; = 20.4%; n\u0026thinsp;=\u0026thinsp;3; 910 participants; CoE very low) (Supplementary data).\u003c/p\u003e\u003cp\u003eWhen evaluating the additional use of uterotonics in women with risk factors, it was determined that TXA likely results in a large reduction in the need for additional uterotonics (RR\u0026thinsp;=\u0026thinsp;0.37; 95% CI 0.24 to 0.58; I\u0026sup2; = 49.7%; p\u0026thinsp;=\u0026thinsp;0.06, n\u0026thinsp;=\u0026thinsp;7; 1498 participants; CoE moderate) (Fig.\u0026nbsp;4C). The evidence suggests that TXA leads to a large reduction in the need for blood transfusions in women with high-risk pregnancies undergoing C-section (RR\u0026thinsp;=\u0026thinsp;0.30; 95% CI 0.22 to 0.40; I\u0026sup2; = 0.0%; n\u0026thinsp;=\u0026thinsp;8; 1698 participants; CoE low) (Fig.\u0026nbsp;4D). Finally, for surgical intervention for postpartum hemorrhage, TXA likely slightly reduces the need for additional surgical intervention (RR\u0026thinsp;=\u0026thinsp;0.35; 95% CI 0.16 to 0.78; I\u0026sup2; = 0.0%; p\u0026thinsp;=\u0026thinsp;0.35; n\u0026thinsp;=\u0026thinsp;2; 260 participants; CoE moderate) (Supplementary data).\u003c/p\u003e\u003cp\u003eWith respect to safety outcomes, the meta-analysis revealed that TXA may have little or no effect on the occurrence of side effects, although the evidence is very uncertain (RR\u0026thinsp;=\u0026thinsp;3.47; 95% CI 0.65 to 18.41; I\u0026sup2; = 91.1%; p\u0026thinsp;=\u0026thinsp;0.00; n\u0026thinsp;=\u0026thinsp;3; 1050 participants; CoE very low) (Supplementary data). Similarly, the certainty of the evidence was also very low in relation to the occurrence of serious adverse events associated with the use of TXA (RR\u0026thinsp;=\u0026thinsp;1.00; 95% CI 0.29 to 3.43; I\u0026sup2; = 0.0%; p\u0026thinsp;=\u0026thinsp;1.00; n\u0026thinsp;=\u0026thinsp;3; 1060 participants) (Supplementary data).\u003c/p\u003e\u003cp\u003e\u003cb\u003eFigure 4.\u003c/b\u003e Meta-analyses of (A) hemoglobin values 48 hours after cesarean section, (B) hematocrit values 48 hours after cesarean section, (C) need for additional uterotonics, and (D) need for blood transfusions.\u003c/p\u003e\u003c/div\u003e"},{"header":"Discussion","content":"\u003cp\u003eThe efficacy and safety of TXA versus placebo for the prevention of PPH in high-risk C-sections were evaluated. Prophylactic TXA use has consistently been shown to be associated with a significant reduction in PPH. The high-risk population allowed for the evaluation of TXA effectiveness, demonstrated efficacy in a wide range of high-risk situations,[\u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e] and expanded the current evidence on the prophylactic use of TXA in high-risk C-sections.[\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e, \u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e]\u003c/p\u003e\u003cp\u003eThe demonstrated effectiveness suggests that the benefits of TXA persist even in the presence of pathophysiological alterations that could interfere with its mechanism of action.[\u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e] However, the efficacy observed in high-risk populations contrasts with the heterogeneous evidence from other pharmacological strategies to prevent PPH.[\u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e, \u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e]\u003c/p\u003e\u003cp\u003eUnlike the WOMAN-2 study, which evaluated TXA as a treatment for established PPH,[\u003cspan citationid=\"CR28\" class=\"CitationRef\"\u003e28\u003c/span\u003e] this research focused on its prophylactic use. It acts before the activation of compensatory mechanisms and hyperfibrinolysis, preventing blood loss and stabilizing clots from the early stages. In contrast, its administration once bleeding has already begun inhibits only active fibrinolysis without stopping the initial hemorrhagic cascade.[\u003cspan citationid=\"CR29\" class=\"CitationRef\"\u003e29\u003c/span\u003e]\u003c/p\u003e\u003cp\u003eCurrent recommendations for the management of PPH state that the use of TXA should be considered when initial therapies fail to control bleeding,[\u003cspan citationid=\"CR30\" class=\"CitationRef\"\u003e30\u003c/span\u003e] that TXA should be administered within three hours of delivery immediately after bleeding begins,[\u003cspan citationid=\"CR31\" class=\"CitationRef\"\u003e31\u003c/span\u003e] or that its use should be part of the initial management of established PPH, alongside uterotonics and mechanical measures.[\u003cspan citationid=\"CR30\" class=\"CitationRef\"\u003e30\u003c/span\u003e] However, the evidence suggests reconsidering these guidelines to include prophylactic use in high-risk populations and to standardize the timing and dosage, as 1 g intravenously is sufficient to inhibit fibrinolysis, whereas 0.5 g does not produce a significant effect.[\u003cspan citationid=\"CR32\" class=\"CitationRef\"\u003e32\u003c/span\u003e]\u003c/p\u003e\u003cp\u003eCompared with the placebo, the use of TXA was associated with a reduction in total blood loss. However, heterogeneity was considerable and explained by the timing of drug administration. Subgroup analysis revealed that the administration of TXA between 10 and 20 minutes before the skin incision was associated with a significant reduction in blood loss, with less heterogeneity. This timing allows for more homogeneous and optimal plasma concentrations during the postpartum fibrinolytic activation period,[\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e] which is activated during the peripartum period.[\u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e] However, the optimal time of administration remains a topic of research, and further studies on the pharmacokinetics and pharmacodynamics in relation to the effect on bleeding are needed.\u003c/p\u003e\u003cp\u003eEvaluations of bleeding during the first two hours after C-section showed that TXA was effective, significantly reducing blood loss in the hours following the procedure.[\u003cspan citationid=\"CR33\" class=\"CitationRef\"\u003e33\u003c/span\u003e] Yang \u003cem\u003eet al.\u003c/em\u003e, (2023) also reported a significant reduction in bleeding two hours after C-section, the peak effect of TXA (with a half-life of approximately three hours),[\u003cspan citationid=\"CR33\" class=\"CitationRef\"\u003e33\u003c/span\u003e] during which time women at risk remain susceptible to secondary bleeding.[\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e, \u003cspan citationid=\"CR34\" class=\"CitationRef\"\u003e34\u003c/span\u003e, \u003cspan citationid=\"CR35\" class=\"CitationRef\"\u003e35\u003c/span\u003e]\u003c/p\u003e\u003cp\u003eThe amount of perioperative blood loss also significantly differed in favor of TXA. This effect is probably due to the antifibrinolytic action of TXA during the critical hours of the perioperative period.[\u003cspan citationid=\"CR33\" class=\"CitationRef\"\u003e33\u003c/span\u003e] Similar findings have been reported, showing that the use of a drug is associated with a reduction in the need for transfusions and the risk of severe bleeding.[\u003cspan additionalcitationids=\"CR37 CR38 CR39\" citationid=\"CR36\" class=\"CitationRef\"\u003e36\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR40\" class=\"CitationRef\"\u003e40\u003c/span\u003e]\u003c/p\u003e\u003cp\u003eIn relation to blood loss exceeding 1000 mL, TXA was associated with a significant reduction in bleeding, significantly reducing the need for surgical interventions, from conservative techniques such as uterine packing to more invasive procedures such as arterial embolization, hemostatic ligatures, and postpartum hysterectomy.[\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e, \u003cspan citationid=\"CR41\" class=\"CitationRef\"\u003e41\u003c/span\u003e] It significantly reduces the need for transfusions, demonstrating its effectiveness in controlling bleeding, supported by better maintenance of hematocrit and hemoglobin postsurgery in favor of the drug,[\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e, \u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e, \u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e, \u003cspan citationid=\"CR41\" class=\"CitationRef\"\u003e41\u003c/span\u003e] reducing the costs associated with transfusions and decreasing the risks inherent in the procedure.[\u003cspan citationid=\"CR42\" class=\"CitationRef\"\u003e42\u003c/span\u003e]\u003c/p\u003e\u003cp\u003eThese findings are consistent with results reported by other authors, who support its use as a prophylactic intervention to prevent severe PPH, especially in high-risk women,[\u003cspan citationid=\"CR43\" class=\"CitationRef\"\u003e43\u003c/span\u003e] and the need for additional interventions such as complementary uterotonics, surgery, and blood transfusions.[\u003cspan additionalcitationids=\"CR37 CR38 CR39\" citationid=\"CR36\" class=\"CitationRef\"\u003e36\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR40\" class=\"CitationRef\"\u003e40\u003c/span\u003e] A lower need for complementary uterotonics was observed, and TXA can effectively complement these strategies through its mechanism of action, allowing for a synergistic effect in the management and prevention of PPH.[\u003cspan citationid=\"CR41\" class=\"CitationRef\"\u003e41\u003c/span\u003e]\u003c/p\u003e\u003cp\u003eThe safety assessment revealed no significant differences in the frequency of side effects between TXA and the placebo. Mild events were generally self-limiting and manageable in the perioperative setting, and no differences were observed between groups regarding serious events, which is consistent with previous findings and supports the safety profile of TXA for obstetric prophylaxis.[\u003cspan citationid=\"CR42\" class=\"CitationRef\"\u003e42\u003c/span\u003e, \u003cspan citationid=\"CR44\" class=\"CitationRef\"\u003e44\u003c/span\u003e]\u003c/p\u003e\u003cp\u003eEvidence indicates that TXA is safe during pregnancy and lactation. A meta-analysis of more than 19,000 participants revealed no significant adverse effects in newborns, and drug levels in breast milk accounted for only 1% of maternal serum levels. There were no differences in long-term outcomes, including neurological development, general health, and infant mortality. Occasional complications, such as low birth weight or preterm delivery, are related to maternal conditions rather than the drug. Therefore, breastfeeding is considered safe, and the U.S. Food and Drug Administration classifies TXA as category B during pregnancy.[\u003cspan citationid=\"CR45\" class=\"CitationRef\"\u003e45\u003c/span\u003e]\u003c/p\u003e\u003cp\u003eThe main limitation of this study is its lack of representativeness, since most studies are from specific regions, making it difficult to generalize the results to different clinical contexts. However, the greatest strength of the study is its contribution to the available evidence through specific research in high-risk women, where the clinical, pathophysiological, and risk factors influencing PPH were examined in detail.\u003c/p\u003e\u003cp\u003eResearch on TXA in obstetrics is needed to optimize its efficacy and safety, determine the optimal dose, evaluate different regimens and routes of administration, and compare prophylactic and therapeutic approaches. Multicenter trials that stratify patients by risk factors are also needed to evaluate effectiveness in different subgroups. Research is also needed on long-term safety, effects on breastfeeding, and the development of predictive biomarkers. Similarly, the integration of artificial intelligence models is necessary to enable personalized PPH prevention, optimize treatment efficacy, and reduce associated risks and costs.\u003c/p\u003e"},{"header":"Conclusion","content":"\u003cp\u003eTXA, as a prophylactic intervention, has consistent and clinically significant benefits in reducing blood loss in high-risk C-sections. This can result in a large reduction in total blood loss in patients undergoing C-section and probably reduces blood loss between 15 and 20 minutes before skin incision, with a more homogeneous effect and a significant reduction in heterogeneity between studies.\u003c/p\u003e\u003cp\u003eAn early reduction in blood loss is likely to result in a large decrease at two hours post-operatively, as well as a large reduction in intraoperative loss and in cases with hemorrhage greater than 1000 mL. In terms of hematological parameters, TXA probably reduces the postoperative decrease in hemoglobin and results in a reduced risk of a decrease in hematocrit, which reinforces the effectiveness of PPH prevention. It also probably results in a large reduction in the additional use of uterotonics and the need for blood transfusions and may reduce the need for complementary surgical interventions to control bleeding.\u003c/p\u003e"},{"header":"Abbreviations","content":"\u003cp\u003ePPH: Postpartum hemorrhage\u003c/p\u003e\n\u003cp\u003eC-section: Cesarean section\u003c/p\u003e\n\u003cp\u003eTXA: Tranexamic acid\u003c/p\u003e\n\u003cp\u003eMD: Mean difference\u003c/p\u003e\n\u003cp\u003eSMD: Standardized mean difference\u003c/p\u003e\n\u003cp\u003eCI: Confidence interval\u003c/p\u003e\n\u003cp\u003eRR: Relative risk\u003c/p\u003e\n\u003cp\u003eEBL: Estimated blood loss\u003c/p\u003e\n\u003cp\u003eCoE: Certainty of evidence\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eEthics approval and consent to participate\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNot applicable\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConsent for publication\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAll authors consent to the publication of the manuscript.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAvailability of data and materials\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNo datasets were generated or analyzed during the current study.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCompeting interests\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors declare that they have no competing interests.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthors\u0026apos; contributions\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eConceptualization: X.S.L., and D.A.T.; Methodology: D.A.T.; Software: D.A.T.; Validation: X.S.L., H.C.G., and D.A.T.; Formal analysis: H.C.G., C.M.G., and D.A.T.; Investigation: X.S.L., H.C.G., C.M.G., K.V.A., Z.I.A., and D.A.T.; Resources: D.A.T.; Data curation: D.A.T.; Writing original draft: H.C.G., C.M.G., and D.A.T.; Writing review and editing: X.S.L., H.C.G., C.M.G., K.V.A., Z.I.A., and D.A.T.; Visualization: H.C.G., D.A.T.; Supervision: D.A.T.; Project administration: D.A.T.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAcknowledgments\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eWe thank Dr. Josu\u0026eacute; Ramos and Jorge Llanes, M.A for reviewing the translation and grammar of the manuscript.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003cstrong\u003eAuthors\u0026apos; information\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNational Institute of Health, San Salvador, El Salvador\u003c/p\u003e\n\u003cp\u003eXochitl Sandoval L\u0026oacute;pez, Hazel C. Garc\u0026iacute;a, Cesar M. Gavidia, Karina V. Alam, Zaida I. \u0026Aacute;lvarez, and David A. Tejada\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;\u003cstrong\u003eCorresponding author:\u0026nbsp;\u003c/strong\u003eDavid A. Tejada\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eEmail:\u0026nbsp;\u003c/strong\[email protected]\u0026nbsp;\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n\u003cli\u003eGiouleka S, Tsakiridis I, Kalogiannidis I, Mamopoulos A, Tentas I, Athanasiadis A, \u003cem\u003eet al\u003c/em\u003e. Postpartum Hemorrhage: A Comprehensive Review of Guidelines. Obstetrical \u0026amp; Gynecological Survey. 2022; 77 (11): 665\u0026ndash;682. https://doi.org/10.1097/OGX.0000000000001061\u003c/li\u003e\n\u003cli\u003eGong J, Chen Z, Zhang Y, Liu Y, Pu J, Xiong C, \u003cem\u003eet al\u003c/em\u003e. Risk-factor model for postpartum hemorrhage after cesarean delivery: a retrospective study based on 3498 patients. \u003cem\u003eSci. 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Alternative routes to intravenous tranexamic acid for postpartum hemorrhage: A systematic search and narrative review. \u003cem\u003eInt. J. Gynaecol. Obstet.\u003c/em\u003e 2022; 158:p 40\u0026ndash;45. https://doi.org/10.1002/ijgo.14201\u003c/li\u003e\n\u003cli\u003eInternational Federation of Gynecology and Obstetrics, International Confederation of Midwives. Joint statement of recommendation for the use of tranexamic acid for the treatment of postpartum haemorrhage. 2021. Accessed August 14, 2025. Available at: https://www.figo.org/joint-statement-recommendation-tranexamic-acid-treatment-pph\u003c/li\u003e\n\u003cli\u003eAdepoju VA, Adnani QES, Adeniyi MO. 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The Lancet. 2024; 404(10463):p 1657\u0026ndash;1667. https://doi.org/10.1016/S0140-6736(24)02102-0\u003c/li\u003e\n\u003cli\u003eGuinness F, Hanley C, Spring A. Meta-analysis: the prophylactic use of tranexamic acid to reduce blood loss during caesarean delivery.\u003cem\u003e Ir. J. Med. Sci\u003c/em\u003e. 2024; 194:p 311\u0026ndash;322. https://doi.org/10.1007/s11845-024-03834-y\u003c/li\u003e\n\u003cli\u003eTranexamic Acid, in: Drugs Lact. Database Lact. National Institute of Child Health and Human Development, Bethesda (MD), 2006. Accessed August 27, 2025. Available at: http://www.ncbi.nlm.nih.gov/books/NBK501734/\u003c/li\u003e\n\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":true,"hideJournal":true,"highlight":"","institution":"National Institute of Health, San Salvador, El Salvador","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":true,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"Postpartum Hemorrhage, Tranexamic Acid, Cesarean Section, High Risk Pregnancy","lastPublishedDoi":"10.21203/rs.3.rs-7961244/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-7961244/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003e\u003cstrong\u003eBackground\u003c/strong\u003e. Postpartum hemorrhage is a leading cause of maternal morbidity and mortality worldwide, particularly among high-risk women. Tranexamic acid has been used as prophylaxis for postoperative blood loss. This systematic review and meta-analysis evaluated the efficacy and safety of tranexamic acid in preventing postpartum hemorrhage in cesarean sections in high-risk women.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eMethods\u003c/strong\u003e. A systematic review with meta-analysis was performed. \u0026nbsp;The risk of bias was assessed using RoB 2.0. Meta-analyses were performed using a random-effects model, along with subgroup and sensitivity analyses. The GRADE methodology was used to assess the certainty of the evidence.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eResults\u003c/strong\u003e. Ten randomized controlled trials involving 1,811 participants were included. Tranexamic acid substantially reduced total blood loss (SMD = -1.74; 95% CI -3.09 to -0.39), with optimal efficacy when administered 15–20 minutes before incision (SMD = -0.61; 95% CI -0.82 to -0.39). Intraoperative blood loss (SMD = -0.99; 95% CI -1.15 to -0.82), blood loss at two hours (SMD = -0.78; 95% CI -1.21 to -0.35), and blood loss \u0026gt;1000 mL (RR = 0.24; 95% CI 0.14 to 0.41) were also reduced. Hematological outcomes, need for additional uterotonics (RR = 0.37; 95% CI 0.24 to 0.58), blood transfusions (RR = 0.30; 95% CI 0.22 to 0.40), and complementary surgical interventions (RR = 0.35; 95% CI 0.16 to 0.78) were likely reduced. \u003cstrong\u003eConclusions\u003c/strong\u003e. Tranexamic acid as a prophylactic intervention effectively reduces blood loss in high-risk cesarean sections, particularly when administered 15–20 minutes before skin incision. It decreases total and intraoperative blood loss, blood loss at two hours, and cases exceeding 1000 mL. Tranexamic acid also likely reduces postoperative hemoglobin and hematocrit drops, the need for additional uterotonics, blood transfusions, and complementary surgical interventions.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eTrial registration.\u003c/strong\u003e PROSPERO CRD420251087054.\u003c/p\u003e","manuscriptTitle":"Prophylactic use of tranexamic acid to prevent postpartum hemorrhage in high-risk cesarean deliveries: a systematic review and meta-analysis","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-10-29 06:39:09","doi":"10.21203/rs.3.rs-7961244/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"40cf1213-21b1-4803-93f6-147afc680a48","owner":[],"postedDate":"October 29th, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[{"id":56960833,"name":"Maternal \u0026 Fetal Medicine"}],"tags":[],"updatedAt":"2025-10-29T06:39:09+00:00","versionOfRecord":[],"versionCreatedAt":"2025-10-29 06:39:09","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-7961244","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-7961244","identity":"rs-7961244","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}