Tranexamic acid for the prevention and treatment of postpartum hemorrhage in resource-limited settings: a literature review
Annals of medicine and surgery (2012). 2024;86(1):353-360
INTRODUCTION Postpartum haemorrhage is a major cause of maternal morbidity and mortality worldwide. Early recognition and appropriate treatment are crucial for managing postpartum haemorrhage. OBJECTIVES This literature review aimed to evaluate the efficacy of tranexamic acid in the prevention and treatment of postpartum haemorrhage in resource-limited settings. SEARCH METHODS This literature review was conducted based on the Preferred Reporting Items for Systematic Review and Meta-analyses (PRISMA) guidelines. A computerized systematic search of the MEDLINE (PubMed), Google Scholar, and Cochrane databases using a combination of the following Medical Subject Headings (MeSH) terms for PubMed: [(obstetric haemorrhage OR postpartum haemorrhage OR massive obstetric haemorrhage) AND (tranexamic acid OR antifibrinolytic drugs) AND (prophylaxis OR prevention) AND (management OR treatment) AND (resource-limited settings OR resource-limited area OR developing countries)] to find articles published in English since 2010. SELECTION CRITERIA Studies on the obstetric population who underwent vaginal or caesarean delivery, comparing the use of tranexamic acid versus placebo (or no treatment) for treatment (or prevention) of postpartum haemorrhage with the outcome of postpartum haemorrhage rate, blood transfusion requirements, uterotonics requirements, hysterectomy, or mortality were included. RESULT In total, 5315 articles were identified. Following the elimination of duplicates, the methodological quality of 15 studies was evaluated independently, with eligibility determined based on the inclusion and exclusion criteria, as well as outcome variables. Finally, eight articles were included in the review. CONCLUSION This review provides evidence that the administration of tranexamic acid has the potential to decrease the need for blood transfusion, incidence of postpartum haemorrhage, demand for supplementary uterotonics, and maternal morbidity and mortality with marginal adverse effects. Healthcare systems must develop and implement interventions that involve the use of tranexamic acid for the treatment of postpartum haemorrhage in resource-limited settings.
Efficacy and safety of tranexamic acid in prevention of postpartum hemorrhage: a systematic review and meta-analysis of 18,649 patients
BMC pregnancy and childbirth. 2023;23(1):817
BACKGROUND In this meta-analysis, we aimed to update the clinical evidence regarding the efficacy and safety of TXA in the prevention of PPH. METHODS A literature search of PubMed, Scopus, Web of Science, Google Scholar, and Cochrane Library from inception until December 2022 was conducted. We included randomized controlled trials (RCTs) comparing TXA with a placebo among pregnant women. All relevant outcomes, such as total blood loss, the occurrence of nausea and/or vomiting, and changes in hemoglobin, were combined as odds ratios (OR) or mean differences (MD) in the meta-analysis models using STATA 17 MP. RESULTS We included 59 RCTs (18,649 patients) in this meta-analysis. For cesarean birth, TXA was favored over the placebo in reducing total blood loss (MD= -2.11 mL, 95%CI [-3.09 to -1.14], P < 0.001), and occurrence of nausea or/and vomiting (OR = 1.36, 95%CI [1.07 to 1.74], P = 0.01). For vaginal birth, the prophylactic use of TXA was associated with lower total blood loss, and higher occurrence of nausea and/or vomiting (MD= -0.89 mL, 95%CI [-1.47 to -0.31], OR = 2.36, 95%CI [1.32 to 4.21], P = 0.02), respectively. However, there were no differences between the groups in changes in hemoglobin during vaginal birth (MD = 0.20 g/dl, 95%CI [-0.07 to 0.48], P = 0.15). The overall risk of bias among the included studies varies from low to high risk of bias using ROB-II tool for RCTs. CONCLUSIONS This meta-analysis suggested that TXA administration is effective among women undergoing cesarean birth or vaginal birth in lowering total blood loss and limiting the occurrence of PPH. Further clinical trials are recommended to test its efficacy on high-risk populations.
Tranexamic acid for the prevention of postpartum bleeding: Protocol for a systematic review and individual patient data meta-analysis
Gates open research. 2023;7:3
Tranexamic acid (TXA) reduces the risk of death and is recommended as a treatment for women with severe postpartum bleeding. There is hope that giving TXA shortly before or immediately after birth could prevent postpartum bleeding. Extending the use of TXA to prevent harmful postpartum bleeding could improve outcomes for millions of women; however we must carefully consider the balance of benefits and potential harms. This article describes the protocol for a systematic review and individual patient data (IPD) meta-analysis to assess the effectiveness and safety of TXA for preventing postpartum bleeding in all women giving birth, and to explore how the effects vary by underlying risk and other patient characteristics. Methods: We will search for prospectively registered, randomised controlled trials involving 500 patients or more assessing the effects of TXA in women giving birth. Two authors will extract data and assess risk of bias. IPD data will be sought from eligible trials. Primary outcomes will be life-threatening bleeding and thromboembolic events. We will use a one-stage model to analyse the data. Subgroup analyses will be conducted to explore whether the effectiveness and safety of TXA varies by underlying risk, type birth, maternal haemoglobin (Hb), and timing of TXA. This protocol is registered on PROSPERO (CRD42022345775). Conclusions: This systematic review and IPD meta-analysis will address important clinical questions about the effectiveness and safety of the use of TXA for the prevention of postpartum bleeding that cannot be answered reliably using aggregate data and will inform the decision of who to treat. PROSPERO registration: CRD42022345775 Keywords Anti-fibrinolytics; Tranexamic acid; childbirth; postpartum haemorrhage; meta-analysis.
Effect of preoperative prophylactic intravenous tranexamic acid on perioperative blood loss control in patients undergoing cesarean delivery: a systematic review and meta-analysis
BMC pregnancy and childbirth. 2023;23(1):420
BACKGROUND Postpartum hemorrhage (PPH) is one of the important risk factors leading to maternal mortality and intervention is essential. Oxytocin therapy is widely used clinically, but the effect is unsatisfactory. The efficacy of tranexamic acid (TXA) in hemostasis is notable, whereas its use in preventing PPH warrants exploration. AIMS To evaluate the effect of prophylactic administration of TXA on perioperative blood loss in women undergoing cesarean section by systematic review and meta-analysis of published studies. METHODS Bibliographic databases were screened from their inception to December 2022 to retrieve relevant studies. Study outcomes including blood loss during cesarean section, 2-h postpartum blood loss, total blood loss (during cesarean section and 2-h postpartum), and 6-h postpartum, as well as hemoglobin changes were extracted and compared. RESULTS A total of 21 studies, nine randomized clinical trials and 12 cohort studies, involving 1896 patients given TXA prophylactically and 1909 patients given placebo or no treatment, were analyzed. Compared with the control group, the preoperative prophylactic intravenous administration of TXA significantly reduced the intraoperative (RCT: P < 0.00001, cohort studies: P < 0.00001), 2-h postpartum (RCT: P = 0.02, cohort studies: P < 0.00001) and total blood loss (RCT: P < 0.00001, cohort studies: P = 0.0002), and reduced the decline in hemoglobin (RCT: P < 0.00001, cohort studies: P = 0.0001), but did not significantly affect blood loss at 6-h postpartum (P = 0.05). CONCLUSION Prophylactic intravenous TXA before cesarean section is helpful in preventing perioperative bleeding in women. TRIAL REGISTRATION http://www.crd.york.ac.uk/PROSPERO , identifier: CRD 42022363450.
Use of tranexamic acid (TXA) to reduce preterm birth and other adverse obstetrical outcomes among pregnant individuals with placenta previa: a systematic review protocol
BMJ open. 2023;13(3):e068892
INTRODUCTION Placenta previa is a placental implantation pathology where the placenta overlies the internal endocervical os. Placenta previa affects approximately 4 per 1000 pregnancies and increases the risk of antepartum bleeding, emergent preterm labour and emergency caesarean sections. Currently, placenta previa is managed through expectant management. Guidelines primarily revolve around the mode and timing of delivery, in-hospital admissions and surveillance. However, the methods to prolong pregnancy have not proven to be clinically effective. Tranexamic acid (TXA), an antifibrinolytic agent, is effectively used to prevent and treat postpartum haemorrhage as well as menorrhagia, with limited adverse effect, and may prove to be an effective treatment for placenta previa. The objective of this systematic review protocol is to review and synthesise the evidence of TXA use for antepartum haemorrhage in placenta previa. METHODS AND ANALYSIS Preliminary searches were conducted on 12 July 2022. We will search MEDLINE, EMBASE, CINAHL, Scopus and the Cochrane Central Register of Controlled Trials. Grey literature resources such as clinical trials registries (ClinicalTrials.gov and the WHO's International Clinical Trials Registry) and preprint servers (Europe PMC and Open Science Framework) will also be searched. The search terms will comprise of index headings and keyword searches related to TXA and the placenta or antepartum bleeding. Cohort and randomised and non-randomised trials will be considered. The target population is pregnant people, of any age, with placenta previa. The intervention is TXA given in the antepartum period. The main outcome of interest is preterm birth before 37 weeks, however, all perinatal outcomes will be collected. Title and abstract will be screened by two reviewers and any conflict will be discussed and evaluated by a third reviewer. The literature will be summarised in narrative form. ETHICS AND DISSEMINATION No ethics approval is required for this protocol. Findings will be disseminated through peer-review publication, lay summaries and conference presentations. PROSPERO REGISTRATION NUMBER CRD42022363009).
Tranexamic acid for the prevention of blood loss after cesarean section: an updated systematic review and meta-analysis of randomized controlled trials
American journal of obstetrics & gynecology MFM. 2023;:101049
OBJECTIVE Tranexamic acid (TXA) is a cost-effective intervention for the prevention of postpartum hemorrhage (PPH) in women undergoing cesarean section but the evidence to support its use is conflicting. We conducted this meta-analysis to evaluate the efficacy and safety of TXA in low- and high-risk cesarean deliveries. DATA SOURCES We searched MEDLINE (via PubMed), Embase, the Cochrane Library, ClinicalTrials.gov, and WHO International Clinical Trials Registry Platform (ICTRP) portal from inception to April 2022 (updated October 2022 and February 2023) with no language restrictions. Additionally, grey literature sources were also explored. STUDY ELIGIBILITY CRITERIA All randomized controlled trials (RCTs) investigating the prophylactic use of intravenous TXA in addition to standard uterotonic agents in women undergoing cesarean deliveries as compared to placebo, standard treatment, or prostaglandins were included in this meta-analysis. METHODS We used the revised Cochrane "Risk of Bias" tool (RoB 2.0) to assess the quality of included RCTs. RevMan 5.4 was used to conduct all statistical analyses under a random-effects model. RESULTS We included 50 RCTs (6 in only high-risk patients and 2 with prostaglandins as the comparator) evaluating TXA in our meta-analysis. TXA reduced the risk of blood loss >1000 mL, mean total blood loss, and the need for blood transfusion in both low- and high-risk patients. TXA was associated with a beneficial effect in our secondary outcomes including decline in hemoglobin levels and the need for additional uterotonic agents. TXA increased the risk of non-thromboembolic adverse events but, based on limited data, did not increase the incidence of thromboembolic events. The administration of TXA before skin incision, but not after cord clamping, was associated with a large benefit. The quality of evidence was rated as low to very low for outcomes in the low-risk population and moderate for most outcomes in the high-risk subgroup. CONCLUSIONS TXA may reduce the risk of blood loss in cesarean deliveries with a higher benefit observed in high-risk patients but the lack of high-quality evidence precludes any strong conclusions. Additional studies, especially in the high-risk population and evaluating the timing of TXA administration, are needed to confirm or refute these findings.
Prophylactic Tranexamic Acid Prevents Postpartum Hemorrhage and Transfusions in Cesarean Deliveries: A Systematic Review and Meta-analysis
American journal of perinatology. 2023
INTRODUCTION Postpartum hemorrhage (PPH) is the leading cause of maternal mortality worldwide and PPH resulting in transfusion is the most common maternal morbidity in the United States. Literature demonstrates that tranexamic acid (TXA) can reduce blood loss in cesarean deliveries; however, there is little consensus on the impact on major morbidities like PPH and transfusions. OBJECTIVE We conducted a systematic review/meta-analysis of randomized controlled trials (RCTs) to evaluate if administration of prophylactic IV TXA prevents PPH and/or transfusions following low-risk cesarean delivery. METHODS PRISMA guidelines were followed. Five databases were searched: Cochrane, EBSCO, Ovid, PubMed, and ClinicalKey. RCTs published in English between January 2000 and December 2021 were included. Studies compared PPH and transfusions in cesarean deliveries between prophylactic IV TXA and control (placebo or no placebo). The primary outcome was PPH, and the secondary outcome was transfusions. Random effects models were used to calculate effect size (ES) of exposure in Mantel-Haenszel Risk Ratios (RR). All analysis was done at a confidence level (CI) of alpha=0.5. RESULTS Modeling showed that TXA led to significantly less risk of PPH than control (RR: 0.43, 95% CI: 0.28-0.67). The effect on transfusion was comparable (RR: 0.39, 95% CI: 0.21-0.73). Heterogeneity was minimal (I2 = 0%). CONCLUSION Due to the large sample sizes needed, many RCTs are not powered to interpret TXA's effect on PPH and transfusions. Pooling these studies in a meta-analysis allows for more power and analysis but is limited by the heterogeneity of studies. Our results minimize heterogeneity while demonstrating that prophylactic TXA reduces the risk for PPH and transfusion. This has the potential to address blood shortages, transfusion-associated risks, and healthcare costs. We suggest considering prophylactic IV TXA as the standard of care in low-risk cesarean deliveries.
Use of tranexamic acid in decreasing blood loss during and after delivery among women in Africa: a systematic review and meta-analysis
Archives of gynecology and obstetrics. 2022
BACKGROUND Africa is a developing continent with a high maternal mortality rate. It is beneficial to implement interventions that alleviate the problem. As a result, this systematic review and meta-analysis was carried out to summarize evidence that will assist concerned bodies in proposing strategies to reduce maternal mortality due to post-partum hemorrhage. METHODS This systematic review and meta-analysis includes randomized control trials (RCT) studies searched from various databases (PubMed, Web of Sciences, SCOPUS, African Journal Online, Clinical trials, and African indexes Medics). Data synthesis and statistical analysis were conducted using a combination of review manager 5.3 and STATA Version 14 software. The effect measure utilized was the standardized mean difference for estimated mean blood loss and mean hemoglobin level. RESULTS This systematic review and meta-analysis includes a total of 3308 women. The pooled standardized mean difference showed that tranexamic acid statistical significantly reduced the estimated amount of blood loss after vaginal delivery (standardized mean difference with 95% CI - 0.93 [- 1.45, - 0.41]) and during and after cesarean delivery (standardized mean difference with 95% CI - 1.93 [- 2.40, - 1.47]). CONCLUSION Tranexamic acid has been found to be a good choice for reducing blood loss during and after delivery in Africa regardless of the mode of delivery. Tranexamic acid had no effect on hemoglobin levels before and after delivery. To reduce maternal mortality due to post-partum hemorrhage, it is critical to implement and strengthen interventions aimed at increasing tranexamic acid uptake in Africa.
Prophylactic tranexamic acid among women undergoing vaginal delivery to reduce postpartum blood loss and related morbidities: a systematic review and meta-analysis of 17 randomized controlled trials
Journal of gynecology obstetrics and human reproduction. 2022;:102378
OBJECTIVE To conduct a systematic review and meta-analysis of all randomized controlled trials (RCTs) that inspected the efficacy and safety of prophylactic TXA compared with control (placebo/no treatment) among women undergoing vaginal delivery on reducing postpartum blood loss and related morbidities. METHODS Six databases were screened from inception until 06-December-2021. The pooled data were summarized as mean difference or risk ratio, respectively, with 95% confidence interval in a fixed- or random-effects model. RESULTS Sixteen studies comprising 17 RCT treatment arms were included. There were 7075 patients; 3548 and 2537 patients were allocated to prophylactic TXA and control groups, respectively. Overall, the included RCTs had a low risk of bias. Prophylactic TXA correlated with a significant decrease in mean postpartum blood loss and mean change in hemoglobin/hematocrit. Moreover, prophylactic TXA was linked to decreased incidence rates of postpartum hemorrhage, need for blood transfusion, and need for additional uterotonic agents. Nevertheless, prophylactic TXA culminated in significantly higher incidence rates of nausea, vomiting, and diarrhea, all of which were well-tolerated. There was no increased risk of thromboembolic events. Leave-one-out sensitivity analysis confirmed the robustness of efficacy endpoints. There was no publication bias for the endpoint of mean postpartum blood loss. CONCLUSION Among patients undergoing vaginal delivery, prophylactic TXA during active management of third stage of labor (AMTSL) appeared largely safe and correlated with a significant decrease in postpartum blood loss and related morbidities compared with control intervention. Prophylactic TXA should be integrated as a "formal" component of AMTSL among women undergoing vaginal delivery.
Prophylactic tranexamic acid to reduce blood loss and related morbidities during hysterectomy: a systematic review and meta-analysis of randomized controlled trials
Obstetrics & gynecology science. 2022
To perform a systematic review and meta-analysis of all randomized controlled trials (RCTs) that evaluated the efficacy and safety of prophylactic tranexamic acid (TXA) versus a control (placebo or no treatment) during hysterectomy for benign conditions. Six databases were screened from inception to January 23, 2022. Eligible studies were assessed for risk of bias. Outcomes were summarized as weighted mean differences and risk ratios with 95% confidence intervals in a random-effects model. Five studies, comprising six arms and 911 patients were included in the study. Two and three studies had an overall unclear and low risk of bias, respectively. Estimated intraoperative blood loss, requirement for postoperative blood transfusion, and requirement for intraoperative topical hemostatic agents were significantly reduced in a prophylactic TXA group when compared with a control group. Moreover, postoperative hemoglobin level was significantly higher in the prophylactic TXA group than in the control group. Conversely, the frequency of self-limiting nausea and vomiting was significantly higher in the prophylactic TXA group than in the control group. There were no significant differences between the groups in terms of surgery duration, hospital stay, and diarrhea rate. All the RCTs reported no incidence of major adverse events in either group, such as mortality, thromboembolic events, visual disturbances, or seizures. There was no publication bias for any outcome, and leave-one-out sensitivity analyses demonstrated stability of the findings. Among patients who underwent hysterectomy for benign conditions, prophylactic TXA appeared largely safe and correlated with substantial reductions in estimated intraoperative blood loss and related morbidities.