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Tranexamic acid for the prevention of blood loss after cesarean section: an updated systematic review and meta-analysis of randomized controlled trials
Cheema, H. A., Ahmad, A. B., Ehsan, M., Shahid, A., Ayyan, M., Azeem, S., Hussain, A., Shahid, A., Nashwan, A. J., MikušPh, D. M., et al
American journal of obstetrics & gynecology MFM. 2023;:101049
Abstract
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.
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Prophylactic Tranexamic Acid Prevents Postpartum Hemorrhage and Transfusions in Cesarean Deliveries: A Systematic Review and Meta-analysis
Lee, A. L., Wang, M., Roy, D., Wang, J., Gokhale, A., Miranda-Cacdac, L., Kuntz, M., Grover, B., Gray, K. M., Curley, K.
American journal of perinatology. 2023
Abstract
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.
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Effect of preoperative prophylactic intravenous tranexamic acid on perioperative blood loss control in patients undergoing cesarean delivery: a systematic review and meta-analysis
Yang, F., Wang, H., Shen, M.
BMC pregnancy and childbirth. 2023;23(1):420
Abstract
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.
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Prophylactic tranexamic acid to reduce blood loss and related morbidities during hysterectomy: a systematic review and meta-analysis of randomized controlled trials
Abu-Zaid A, Baradwan S, Badghish E, AlSghan R, Ghazi A, Albouq B, Khadawardi K, AlNaim NF, AlNaim LF, Fodaneel M, et al
Obstetrics & gynecology science. 2022
Abstract
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.
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Prophylactic tranexamic acid during myomectomy: A systematic review and meta-analysis of randomized controlled trials
Baradwan S, Hafidh B, Latifah HM, Gari A, Sabban H, Abduljabbar HH, Tawfiq A, Hakeem GF, Alkaff A, AlSghan R, et al
European journal of obstetrics, gynecology, and reproductive biology. 2022;276:82-91
Abstract
OBJECTIVE To conduct a systematic review and meta-analysis of randomized controlled trials on the clinical efficacy and safety of prophylactic tranexamic acid (TXA) versus control (normal saline/no treatment) during myomectomy. METHODS Six databases were screened from inception until 21-February-2022. The eligible studies were assessed for risk of bias. The outcomes were summarized as mean difference (MD) and risk ratio (RR) with 95% confidence intervals (CI) in a random-effects model. RESULTS Seven studies, comprising eight arms and 571 patients (TXA = 304 patients, control = 267 patients) were analyzed. The included studies had an overall low risk of bias. The mean intraoperative blood loss (MD = -224.34 ml, 95% CI [-303.06, -145.61], p < 0.001), mean postoperative blood loss, and mean total blood loss were significantly reduced in favor of the prophylactic TXA group. Additionally, the mean postoperative hemoglobin (MD = 0.4 mg/dl, 95% CI [0.11, 0.68], p = 0.006) and mean postoperative hematocrit levels were significantly higher in favor of the prophylactic TXA group. While the mean hospital stay was significantly reduced in favor of the prophylactic TXA group (MD = -0.39 d, 95% [-0.74, -0.04], p = 0.03), there was no significant difference between both groups regarding the mean operation time and rate of blood transfusion. None of the participants in both groups developed any incidence of thromboembolic events. The rate of nausea was significantly higher in disfavor of the prophylactic TXA group (RR = 2.68, 95% CI [1.11, 6.43], p = 0.03). CONCLUSION Among patients undergoing myomectomy, prophylactic TXA was largely safe and linked to substantial reductions in perioperative blood loss and related morbidities.
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The Effect of Intravenous Tranexamic Acid on Myomectomy: A Systematic Review and Meta-Analysis of Randomized Controlled Trials
Kathopoulis N, Prodromidou A, Zacharakis D, Chatzipapas I, Diakosavvas M, Kypriotis K, Grigoriadis T, Protopapas A
Journal of personalized medicine. 2022;12(9)
Abstract
Myomectomy is the preferred surgical treatment for symptomatic women with uterine myomas who wish to preserve their fertility. The procedure may be associated with significant intraoperative blood loss, which predisposes to increased transfusion rates and morbidity. The objective of our systematic review and meta-analysis is to investigate whether intravenous (IV) use of tranexamic acid (TXA) may reduce blood loss during myomectomy. Three electronic databases were screened until June 2022. The eligible studies were assessed for risk of bias. Four randomized controlled trials that reported outcomes from a total of 310 women were finally included in the meta-analysis-155 patients received intravenous TXA while the remaining 155 received placebo injection with normal saline or water for injection. Total estimated blood loss was significantly lower in patients who received TXA before myomectomy compared to control (230 patients MD -227.09 mL 95% CI -426.26, -27.91, p = 0.03). This difference in favor of TXA group remained when intraoperative and postoperative blood loss was separately analyzed. Postoperative hematocrit values and hemoglobin levels did not differ among the two groups (180 patients MD 0.67% 95% CI -0.26, 1.59, p = 0.16 and 250 patients MD 0.17 mg/dL 95% CI 0.07, 0.41, p = 0.17, respectively). The number of patients that received blood transfusion was also not different (310 patients OR 0.46 95% CI -0.14, 1.49, p = 0.19). Total operative time was significantly prolonged in control group compared to TXA (310 patients MD -16.39 min 95% CI -31.44, -1.34 p = 0.03). Our data show that the IV use of TXA may significantly reduce intraoperative blood loss in patients undergoing myomectomy and contribute to reduced operative time.
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Tranexamic acid for prevention of bleeding in caesarean Delivery: an overview of systematic reviews
Hurskainen T, Deng MX, Etherington C, Burns J, Martin Calderon L, Moher D, Edwards W, Boet S
Acta anaesthesiologica Scandinavica. 2021
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Editor's Choice
Abstract
BACKGROUND Bleeding is the leading cause of maternal mortality in the world. Tranexamic acid reduces bleeding in trauma and surgery. Several systematic reviews of randomized trials have investigated tranexamic acid in the prevention of bleeding in caesarean delivery. However, the conclusions from systematic reviews are conflicting. This overview aims to summarize the evidence and explore the reasons for conflicting conclusions across the systematic reviews. METHODS A comprehensive literature search of Medline, Embase, and Cochrane Database of Systematic Reviews was conducted from inception to April 2021. Screening, data extraction, and quality assessments were performed by two independent reviewers. A Measurement Tool to Assess Reviews 2 and the Risk of Bias Assessment Tool for Systematic Reviews were used for study appraisal. A qualitative synthesis of evidence is presented. RESULTS Fourteen systematic reviews were included in our analysis. Across these reviews, there were 32 relevant randomized trials. A modest reduction in blood transfusions and bleeding outcomes was found by most systematic reviews. Overall confidence in results varied from low to critically low. All of the included systematic reviews were at high risk of bias. Quality of evidence from randomized trials was uncertain. CONCLUSIONS Systematic reviews investigating prophylactic tranexamic acid in caesarean delivery are heterogeneous in terms of methodological and reporting quality. Tranexamic acid may reduce blood transfusion and bleeding outcomes, but rigorous well-designed research is needed due to the limitations of the included studies. Data on safety and adverse effects is insufficient to draw conclusions.
PICO Summary
Population
Patients undergoing caesarean delivery (14 studies).
Intervention
Overview of systematic reviews on tranexamic acid for the prevention of bleeding.
Comparison
Outcome
A modest reduction in blood transfusions and bleeding outcomes was found by most systematic reviews. Overall confidence in results varied from low to critically low. All of the included systematic reviews were at high risk of bias. Quality of evidence from randomized trials was uncertain.
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Tranexamic acid for the prevention of postpartum hemorrhage in women undergoing cesarean delivery: an updated meta-analysis
Bellos I, Pergialiotis V
American journal of obstetrics and gynecology. 2021
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Editor's Choice
Abstract
OBJECTIVE To assess the efficacy and safety of prophylactic tranexamic acid administration in comparison with standard uterotonic agents alone among women undergoing cesarean delivery. DATA SOURCES Medline, Scopus, Web of Science, Cochrane Central Register of Controlled Trials, Clinicaltrials.gov and Google Scholar were systematically searched from inception to June 30, 2021. STUDY ELIGIBILITY CRITERIA Randomized controlled trials comparing intravenous tranexamic acid administration to placebo in women undergoing cesarean delivery and receiving standard prophylactic uterotonic agents were held eligible. STUDY APPRAISAL AND SYNTHESIS METHODS The risk of bias of individual studies was appraised with the RoB-2 tool. Meta-analysis was conducted by fitting random-effects models using restricted maximum likelihood. Subgroup analysis was performed based on country, protocol availability, double-blinding, risk of bias, sample size and tranexamic acid dose. One-stage meta-analysis was performed as a sensitivity analysis. The credibility of outcomes was appraised with the Grading of Recommendations Assessment, Development and Evaluation approach. RESULTS Overall, 36 studies with 10,659 women were included. Tranexamic acid administration was associated with significantly lower total blood loss (Mean difference-MD: -189.44 ml, 95% confidence intervals-CI: -218.63; -160.25), lower hemoglobin drop (MD: 8.22%, 95% CI: 5.54; 10.90), decreased risk of blood loss >1000 ml (Odds ratio-OR: 0.37, 95% CI: 0.22; 0.60), transfusion requirement (OR: 0.41, 95% CI: 0.26; 0.65) and need of additional uterotonics (OR: 0.36, 95% CI: 0.25; 0.52). Subgroup analysis indicated a greater effect of tranexamic acid on total blood loss reduction in low-middle income countries. The outcomes remained stable by separately evaluating women at low bleeding risk. One-stage meta-analysis demonstrated similar outcomes with the primary analysis. The quality of evidence was judged to be moderate regarding total blood loss and hemoglobin percentage change and low for the other outcomes. CONCLUSIONS This meta-analysis suggests that prophylactic tranexamic acid administration is effective among women undergoing cesarean delivery in lowering postpartum blood loss and limiting hemoglobin drop. Further research is needed to test its efficacy in high-risk populations and to verify its safety profile.
PICO Summary
Population
Women undergoing caesarean delivery (36 studies, n= 10,659).
Intervention
Tranexamic acid.
Comparison
Standard uterotonic agents alone.
Outcome
Tranexamic acid administration was associated with significantly lower total blood loss (Mean difference (MD): -189.44 ml), lower haemoglobin drop (MD: 8.22%), decreased risk of blood loss >1000 ml, transfusion requirement and need of additional uterotonics. Subgroup analysis indicated a greater effect of tranexamic acid on total blood loss reduction in low-middle income countries. The outcomes remained stable by separately evaluating women at low bleeding risk. One-stage meta-analysis demonstrated similar outcomes with the primary analysis. The quality of evidence was judged to be moderate regarding total blood loss and haemoglobin percentage change and low for the other outcomes.
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Tranexamic acid in gynecologic surgery
Zakhari A, Sanders AP, Solnik MJ
Current medical research and opinion. 2019;:1
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Full text
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Editor's Choice
Abstract
Objective: To review the mechanism of action, pharmacology, dosing, and complications of tranexamic acid (TXA) and consolidate current evidence for TXA in gynecologic surgery.Methods: A literature search of PubMed, Ovid (MEDLINE), Google Scholar, and Elsevier was performed, in addition to a targeted search of cited references involving TXA and gynecologic surgery. Preference was given to systematic reviews and randomized control trials (RCTs).Results: TXA reversibly binds to plasminogen, preventing clot degradation. RCTs on hysterectomy, myomectomy, cervical conisation, hysteroscopy, and surgery for cervical and ovarian cancer were identified, as were case reports on TXA use for ectopic pregnancy. During hysterectomy, TXA reduces blood loss (two RCTs, n = 432, mean difference -66.0mL and 180mL), blood transfusion (1 RCT, n = 100, 12% versus 42%, p < 0.00001). For myomectomy, a systematic review and meta-analysis showed a statistically significant decrease in blood loss with TXA (two RCTs, mean difference -213.1mL, 95% CI: -242.4mL to -183.7mL). Following cervical conisation, TXA decreased the risk of delayed hemorrhage (four RCTs, RR 0.23, 95% CI: 0.11 - 0.50). A single RCT for cervical and ovarian cancer surgery demonstrated a decrease mean blood loss of 120mL - 135mL and 210mL, respectively, and fewer blood transfusions for the latter (OR 0.44, upper 95% CI: 0.97, p = 0.02). Less robust data suggest a possible benefit from TXA during hysteroscopy and surgery for ectopic pregnancies. Most commonly, 1g of intravenous TXA is given intraoperatively.Conclusion: TXA is a safe adjunct that can be considered in a variety of gynecologic surgeries to decrease blood loss and risk of blood transfusion.
PICO Summary
Population
Patients undergoing gynaecologic surgery, (9 studies).
Intervention
Tranexamic acid (TXA) in various dosing regimens.
Comparison
Various comparators.
Outcome
During hysterectomy, TXA reduces blood loss (two RCTs, n = 432, mean difference -66.0mL and 180mL), blood transfusion (1 RCT, n = 100, 12% versus 42%). For myomectomy, a systematic review and meta-analysis showed a statistically significant decrease in blood loss with TXA (two RCTs, mean difference -213.1mL). Following cervical conisation, TXA decreased the risk of delayed hemorrhage (four RCTs, RR 0.23). A single RCT for cervical and ovarian cancer surgery demonstrated a decrease mean blood loss of 120mL - 135mL and 210mL, respectively, and fewer blood transfusions for the latter.
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Prophylactic use of tranexamic acid reduces blood loss and transfusion requirements in patients undergoing cesarean section: A meta-analysis
Wang Y, Liu S, He L
The journal of obstetrics and gynaecology research. 2019
Abstract
AIM: Tranexamic acid (TXA) has been used to treat peripartum hemorrhage, while preoperative use of TXA in cesarean section (CS) remains controversial. To assess the effectiveness and safety of prophylactic application of TXA, a meta-analysis was performed. METHODS Electronic databases (MEDLINE [PubMed], Cochrane central register of controlled trials and Embase) were searched up to November 2018. The relevant data and quality of included trail were analyzed by RevMan 5.3. The study was registered at PROSPERO (CRD42018111165). RESULTS Twenty-one randomized controlled trials with a total of 3852 patients were included. Only one research reported thromboembolic events. Compared with control groups, the intra-operative blood loss (mean difference [MD] -155.23 mL, 95% confidence interval [CI] -195.64 - 114.81; P<0.01), postoperative blood loss (MD -26.67 mL, 95% CI -32.98 to -20.36; P<0.01), total blood loss (MD -184.88 mL, 95% CI -218.83 to -150.94; P<0.01), transfusion requirements (relative risk [RR] 0.29, 95% CI 0.18-0.49, P<0.01), massive hemorrhage (RR 0.39, 95% CI 0.30 to 0.51; P<0.01) and additional uterotonic agents use (RR 0.40, 95% CI 0.30-0.55, P<0.01) were markedly reduced in TXA-treated patients. Besides, TXA yielded a significant reduction in hemoglobin drop (MD -0.80 g/dL, 95% CI -1.07 to -0.53; P<0.01) and hematocrit drop (MD -2.05, 95% CI -3.09 to -1.01; P<0.01) compared with control groups. CONCLUSION Prophylactic application of TXA can decrease perioperative blood loss and transfusion requirements in patients undergoing CS. More high-quality researches are needed to determine optimal dose of the drug.