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).
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.
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.
Analysis of the efficacy of prophylactic tranexamic acid in preventing postpartum bleeding: systematic review with meta-analysis of randomized clinical trials
Brazilian journal of anesthesiology (Elsevier). 2022
BACKGROUND Postpartum Hemorrhage (PPH) is one of the main causes of maternal mortality, mainly in the poorest regions of the world, drawing attention to the need for strategies for preventing it. This study aims to evaluate the efficacy of prophylactic administration of Tranexamic Acid (TXA) in decreasing blood loss in pregnant women in delivery, preventing PPH. METHODS Systematic review of randomized clinical trials. We searched for publications in PubMed, EMBASE and Cochrane Library databases, with the uniterms "postpartum, puerperal hemorrhage" and "tranexamic acid", published between January of 2004 and January of 2020. The eligibility criteria were trials published in English with pregnant women assessed during and after vaginal or cesarean delivery about the effect of prophylactic use of TXA on bleeding volume. The random-effects model was applied with the DerSimonian-Laird test and the Mean Difference (MD) was calculated for continuous variables together with each 95% CI. This systematic review was previously registered in the PROSPERO platform under the registration n° CRD42020187393. RESULTS Of the 630 results, 16 trials were selected, including one with two different doses, performing a total of 6731 patients. The intervention group received a TXA dose that varied between 10 mg.kg(-1) and 1g (no weight calculation). The TXA use was considered a protective factor for bleeding (MD: -131.07; 95% CI: -170.00 to -92.78; p = 0.000) and hemoglobin variation (MD: -0.417; 95% CI: -0.633 to -0.202; p = 0.000). In the subgroup analysis related to the cesarean pathway, the effect of TXA was even greater. CONCLUSION The prophylactic use of tranexamic acid is effective in reducing the post-partum bleeding volume. PROSPERO REGISTRATION ID CRD42020187393.
Prophylactic Tranexamic Acid in High-Risk Patients Undergoing Cesarean Delivery: A Systematic Review and Meta-Analysis of Randomized Controlled Trials
Aana j. 2020;88(4):273-281
Scant evidence exists regarding use of tranexamic acid (TXA) in high-risk obstetrics. The aim of this review was to evaluate the efficacy of prophylactic TXA in high-risk patients for postpartum hemorrhage. The review was conducted following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. Only studies examining the effects of TXA compared with placebo in mitigating postpartum hemorrhage were included. The primary outcomes were blood loss intraoperatively and postoperatively. The secondary outcomes were the frequency of additional uterotonic therapy and postoperative hemoglobin concentration. Three trials consisting of 203 patients were included. Compared with placebo, there was a low quality of evidence that TXA may reduce blood loss intraoperatively (mean difference, -361.41; 95% CI, -573.13 to -149.69; P = .0008) and postoperatively (mean difference, -177.95; 95% CI, -296,65 to -59.25; P = .003). We also found a moderate quality of evidence that TXA decreased the number of uterotonic agents used (risk ratio, 0.26; 85% CI, 0.16 to 0.41; P < .00001) but did not affect postoperative hemoglobin level (mean difference, 0.41; 95% CI, -0.08 to 0.90; P = .10). Prophylactic TXA may decrease blood loss and reduce the number of rescue uterotonics in high-risk patients undergoing cesarean delivery.
Tranexamic acid for postpartum hemorrhage prevention in vaginal delivery: A meta-analysis
BACKGROUND Tranexamic acid (TA) has been demonstrated to reduce blood loss and the incidences of postpartum hemorrhage (PPH) during caesarean sections. We compared the clinical efficacy of TA administration on vaginal deliveries with recently published papers. METHODS Electronic databases of PubMed, Cochrane Library, Embase and Chinese CNKI (Chinese database) and Wanfang were searched through November 2019.The randomized controlled trials were selected between TA and control groups. The relevant studies included four trials with a total of 4579 patients. RESULTS Patients treated with TA had a reduction in total blood loss (P = .009), lower postoperative blood loss (P < .00001), a reduced number of PPH (P = .02). However, the occurrence of nausea or/and vomiting is higher in the TA group (the incidence of nausea or vomiting [P < .00001], nausea [P < .00001] and vomiting [P < .00001]). CONCLUSION TA resulted in fewer occurrence rates of PPH, and no significant increase in occurrences of dizziness or photopsia, but higher incidence of vomiting and nausea.
Prophylactic use of tranexamic acid after vaginal delivery reduces the risk of primary postpartum hemorrhage
The journal of maternal-fetal & neonatal medicine : the official journal of the European Association of Perinatal Medicine, the Federation of Asia and Oceania Perinatal Societies, the International Society of Perinatal Obstetricians. 2019;:1-9
BACKGROUND Postpartum hemorrhage (PPH) is responsible for about 25% of maternal deaths worldwide. Antifibrinolytic agents, mainly tranexamic acid, have been demonstrated to reduce maternal blood loss and need for transfusion requirements at delivery in some settings. OBJECTIVE The aim of this meta-analysis of randomized controlled trials (RCTs) was to evaluate the effectiveness of tranexamic acid for the prevention of PPH after vaginal delivery. DATA SOURCES The search was conducted using electronic databases from the inception of each database through February 2018. Review of articles also included the abstracts of all references retrieved from the search. No restrictions for language or geographic location were applied. STUDY DESIGN Selection criteria included RCTs comparing the prophylactic use of tranexamic acid after vaginal delivery with control (either placebo or no treatment). Trials in women undergoing cesarean delivery and trials in women with established PPH were excluded. The primary outcome was the incidence of primary PPH. The summary measures were reported as summary relative risk (RR) with 95% confidence interval (CI) using the random-effects model of DerSimonian and Laird. TABULATION, INTEGRATION, AND RESULTS Four RCTs, including 4671 participants, evaluating tranexamic acid usually 1 g intravenous (IV) within 10 min after vaginal delivery in addition to oxytocin, cord traction, and uterine massage, at or near term for prevention of primary PPH, defined mostly as blood loss ≥500 mL in the first 24 h following delivery, were analyzed. Women who received prophylactic tranexamic acid after vaginal delivery had a significantly lower incidence of primary PPH (8.7 versus 11.4%; RR 0.61, 95% CI 0.41-0.91) and lower mean blood loss mean difference (MD) -84.74 mL, 95% CI -109.76 to -59.72). The risk of thrombotic events was not increased in the tranexamic acid group. CONCLUSIONS Prophylactic tranexamic acid 1 g IV within 10 min after vaginal delivery reduces the risk of primary PPH.
Antifibrinolytic drugs for treating primary postpartum haemorrhage
The Cochrane Database of Systematic Reviews. 2018;2:CD012964
BACKGROUND Postpartum haemorrhage (PPH) - heaving bleeding within the first 24 hours after giving birth - is one of the main causes of death of women after childbirth. Antifibrinolytics, primarily tranexamic acid (TXA), have been shown to reduce bleeding in surgery and safely reduces mortality in trauma patients with bleeding without increasing the risk of adverse events.An earlier Cochrane review on treatments for primary PPH covered all the various available treatments - that review has now been split by types of treatment. This new review concentrates only on the use of antifibrinolytic drugs for treating primary PPH. OBJECTIVES To determine the effectiveness and safety of antifibrinolytic drugs for treating primary PPH. SEARCH METHODS We searched Cochrane Pregnancy and Childbirth's Trials Register, ClinicalTrials.gov, the WHO International Clinical Trials Registry Platform (ICTRP) (28 May 2017) and reference lists of retrieved studies. SELECTION CRITERIA Randomised controlled trials (RCTs), including cluster-randomised trials of antifibrinolytic drugs (aprotinin, TXA, epsilon-aminocaproic acid (EACA) and aminomethylbenzoic acid, administered by whatever route) for primary PPH in women.Participants in the trials were women after birth following a pregnancy of at least 24 weeks' gestation with a diagnosis of PPH, regardless of mode of birth (vaginal or caesarean section) or other aspects of third stage management.We have not included quasi-randomised trials, or cross-over studies. Studies reported as abstracts have not been included if there was insufficient information to allow assessment of risk of bias.In this review we only identified studies looking at TXA. DATA COLLECTION AND ANALYSIS Two review authors independently extracted data from each study using an agreed form. We entered data into Review Manager software and checked for accuracy.For key review outcomes, we rated the quality of the evidence as 'high', 'moderate', 'low' or 'very low' according to the GRADE approach. MAIN RESULTS Three trials (20,412 women) met our inclusion criteria. Two trials (20,212 women) compared intravenous (IV) TXA with placebo or standard care and were conducted in acute hospital settings (labour ward, emergency department) (in high-, middle- and low-income countries).One other trial (involving 200 women) was conducted in Iran and compared IV TXA with rectal misoprostol, but did not report on any of this review's primary or GRADE outcomes. There were no trials that assessed EACA, aprotinin or aminomethylbenzoic acid.Standard care plus IV TXA for the treatment of primary PPH compared with placebo or standard care aloneTwo trials (20,212 women) assessed the effect of TXA for the treatment of primary PPH compared with placebo or standard care alone. The larger of these (The WOMAN trial) contributed over 99% of the data and was assessed as being at low risk of bias. The quality of the evidence varied for different outcomes, Overall, evidence was mainly graded as moderate to high quality.The data show that IV TXA reduces the risk of maternal death due to bleeding (risk ratio (RR) 0.81, 95% confidence interval (CI) 0.65 to 1.00; two trials, 20,172 women; quality of evidence: moderate). The quality of evidence was rated as moderate due to imprecision of effect estimate. The effect was more evident in women given treatment between one and three hours after giving birth with no apparent reduction when given after three hours (< one hour = RR 0.80, 95% CI 0.55 to 1.16; one to three hours = RR 0.60, 95% CI 0.41 to 0.88; > three hours = RR 1.07, 95% 0.76 to 1.51; test for subgroup differences: Chi(2) = 4.90, df = 2 (P = 0.09), I(2) = 59.2%). There was no heterogeneity in the effect by mode of birth (test for subgroup differences: Chi(2) = 0.01, df = 1 (P = 0.91), I(2) = 0%). There were fewer deaths from all causes in women receiving TXA, although the 95% CI for the effect estimate crosses the line of no effect (RR 0.88, 95% CI 0.74 to 1.05; two trials, 20,172 women, quality of evidence: moderate). Results from one trial with 151
Tranexamic acid for treatment of primary postpartum hemorrhage after vaginal delivery: a systematic review and meta-analysis of randomized controlled trials
The Journal of Maternal-Fetal & Neonatal Medicine : the Official Journal of the European Association of Perinatal Medicine, the Federation of Asia and Oceania Perinatal Societies, the International Society of Perinatal Obstetricians. 2018;:1-11.
BACKGROUND Postpartum hemorrhage (PPH) is responsible for about 25% of maternal deaths worldwide. Antifibrinolytic agents, mainly tranexamic acid, have been demonstrated to reduce blood loss in patients with established PPH Objective: The aim of this meta-analysis of randomized controlled trials (RCTs) was to evaluate the effectiveness of tranexamic acid administration in women with established primary PPH after vaginal delivery. DATA SOURCES The search was conducted using electronic databases from inception of each database through February 2018. Review of articles also included the abstracts of all references retrieved from the search. No restrictions for language or geographic location were applied. STUDY DESIGN Selection criteria included RCTs comparing the use of tranexamic acid in women with established primary PPH after vaginal delivery with control (either placebo or no treatment). Trials in women undergoing cesarean delivery and trials in prevention of PPH were excluded. The primary outcome was the incidence of hysterectomy. The summary measures were reported as summary relative risk (RR) with 95% of confidence interval (CI) using the random effects model of DerSimonian and Laird. TABULATION, INTEGRATION, AND RESULTS Two trials including 14 363 women with established primary PPH after vaginal delivery were analyzed. Women who received tranexamic acid soon after the diagnosis of PPH had a significantly lower incidence of hysterectomy (0.5 versus 0.8%; RR 0.63, 95% CI 0.42-0.94), compared to those who did not. The risk of thrombotic events was not increased in the tranexamic acid group. CONCLUSION In women with established PPH after vaginal delivery, use of tranexamic acid reduces the risk of hysterectomy and does not increase the risk of thrombotic events. We recommend 1 g plus a second dose of 1 g if bleeding continues after 30 min.
Women with primary postpartum haemorrhage (PPH) after vaginal delivery (2 studies, n= 14,363).
Tranexamic acid (TXA), (n= 7,165).
Placebo or no treatment (n= 7,198).
Women who received TXA soon after the diagnosis of PPH had a significantly lower incidence of hysterectomy (0.5% vs 0.8%; RR 0.63, 95% CI 0.42-0.94), compared to those who did not. The risk of thrombotic events was not increased in the TXA group.
Antifibrinolytics for heavy menstrual bleeding
The Cochrane Database of Systematic Reviews. 2018;4:CD000249.
BACKGROUND Heavy menstrual bleeding (HMB) is an important physical and social problem for women. Oral treatment for HMB includes antifibrinolytic drugs, which are designed to reduce bleeding by inhibiting clot-dissolving enzymes in the endometrium.Historically, there has been some concern that using the antifibrinolytic tranexamic acid (TXA) for HMB may increase the risk of venous thromboembolic disease. This is an umbrella term for deep venous thrombosis (blood clots in the blood vessels in the legs) and pulmonary emboli (blood clots in the blood vessels in the lungs). OBJECTIVES To determine the effectiveness and safety of antifibrinolytic medications as a treatment for heavy menstrual bleeding. SEARCH METHODS We searched the Cochrane Gynaecology and Fertility (CGF) Group trials register, CENTRAL, MEDLINE, Embase, PsycINFO and two trials registers in November 2017, together with reference checking and contact with study authors and experts in the field. SELECTION CRITERIA We included randomized controlled trials (RCTs) comparing antifibrinolytic agents versus placebo, no treatment or other medical treatment in women of reproductive age with HMB. Twelve studies utilised TXA and one utilised a prodrug of TXA (Kabi). DATA COLLECTION AND ANALYSIS We used standard methodological procedures expected by Cochrane. The primary review outcomes were menstrual blood loss (MBL), improvement in HMB, and thromboembolic events. MAIN RESULTS We included 13 RCTs (1312 participants analysed). The evidence was very low to moderate quality: the main limitations were risk of bias (associated with lack of blinding, and poor reporting of study methods), imprecision and inconsistency.Antifibrinolytics (TXA or Kabi) versus no treatment or placeboWhen compared with a placebo, antifibrinolytics were associated with reduced mean blood loss (MD -53.20 mL per cycle, 95% CI -62.70 to -43.70; I(2) = 8%; 4 RCTs, participants = 565; moderate-quality evidence) and higher rates of improvement (RR 3.34, 95% CI 1.84 to 6.09; 3 RCTS, participants = 271; moderate-quality evidence). This suggests that if 11% of women improve without treatment, 43% to 63% of women taking antifibrinolytics will do so. There was no clear evidence of a difference between the groups in adverse events (RR 1.05, 95% CI 0.93 to 1.18; 1 RCT, participants = 297; low-quality evidence). Only one thromboembolic event occurred in the two studies that reported this outcome.TXA versus progestogensThere was no clear evidence of a difference between the groups in mean blood loss measured using the Pictorial Blood Assessment Chart (PBAC) (MD -12.22 points per cycle, 95% CI -30.8 to 6.36; I(2) = 0%; 3 RCTs, participants = 312; very low quality evidence), but TXA was associated with a higher likelihood of improvement (RR 1.54, 95% CI 1.31 to 1.80; I(2) = 32%; 5 RCTs, participants = 422; low-quality evidence). This suggests that if 46% of women improve with progestogens, 61% to 83% of women will do so with TXA.Adverse events were less common in the TXA group (RR 0.66, 95% CI 0.46 to 0.94; I(2) = 28%; 4 RCTs, participants = 349; low-quality evidence). No thromboembolic events were reported in any group.TXA versus non-steroidal anti-inflammatory drugs (NSAIDs)TXA was associated with reduced mean blood loss (MD -73.00 mL per cycle, 95% CI -123.35 to -22.65; 1 RCT, participants = 49; low-quality evidence) and higher likelihood of improvement (RR 1.43, 95% CI 1.18 to 1.74; 1(2) = 0%; 2 RCTs, participants = 161; low-quality evidence). This suggests that if 61% of women improve with NSAIDs, 71% to 100% of women will do so with TXA. Adverse events were uncommon and no comparative data were available. No thromboembolic events were reported.TXA versus ethamsylateTXA was associated with reduced mean blood loss (MD 100 mL per cycle, 95% CI -141.82 to -58.18; 1 RCT, participants = 53; low-quality evidence), but there was insufficient evidence to determine whether the groups differed in rates of improvement (RR 1.56, 95% CI 0.95 to 2.55; 1 RCT, participants = 53; very low quality evidence) or