Tranexamic acid for the prevention and the treatment of primary postpartum haemorrhage: a systematic review
Journal of obstetrics and gynaecology : the journal of the Institute of Obstetrics and Gynaecology. 2022;:1-13
Tranexamic acid (TA) has been proposed for preventing or treating primary postpartum haemorrhage (PPH), which is the leading cause of maternal morbidity and mortality worldwide. We conducted a systematic literature search to the TA role in managing PPH in vaginal and caesarean delivery. Twenty-seven randomised controlled trials (RCTs) (33,302 women) were identified. Three RCTs investigated TA for preventing PPH after vaginal delivery and 22 after caesarean section. None demonstrated a preventive effect on secondary clinical outcomes related to blood loss. Two trials evaluated TA for treating PPH after vaginal and caesarean delivery. Only the WOMAN trial showed that 1 g of TA is effective. In conclusion, TA is considered useful and is recommended or advised for treating PPH. Conversely, available evidence on the prophylactic role is still limited, and this use is not supported. Further investigation is recommended. In this regard, stronger and more reliable outcomes than blood loss should be considered.
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 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.
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
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
BET 1: Intravenous tranexamic acid for the treatment of post-partum haemorrhage
Emergency Medicine Journal : Emj. 2018;35((8)):523-524.
A short-cut review was carried out to see if administering tranexamic acid reduced mortality in patients with postpartum haemorrhage. The author, date and country of publication, patient group studied, study type, relevant outcomes, results, and study weaknesses of these papers are tabulated. Two randomised controlled trials were found, a smaller one suggesting that treatment with tranexamic acid reduced the volume of blood lost and a much larger study that showed a reduction in mortality due to bleeding in this patient group. There were no significant side effects from this treatment found in either study.
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.
Safety and efficacy of tranexamic acid for prevention of obstetric haemorrhage: an updated systematic review and meta-analysis
Blood Transfusion = Trasfusione Del Sangue. 2018;:1-10.
BACKGROUND A number of clinical systematic review and meta-analysis have been published on the use of tranexamic in the obstetric setting. The aim of this meta-analysis was to evaluate the safety and effectiveness of tranexamic acid in reducing blood loss when given prior to caesarean delivery. MATERIALS AND METHODS We searched the Cochrane Wounds Specialized Register, Cochrane Central, MEDLINE (through PUBMED), Embase, and SCOPUS electronic databases. We also searched clinical trials registries for ongoing and unpublished studies, and checked reference lists to identify additional studies. We used no restrictions with respect to language and date of publication. Two review authors independently performed study selection, "Risk of bias" assessment, and data extraction. Initial disagreements were resolved by discussion, or by including a third review author when necessary. RESULTS We found 18 randomised controlled trials (RCTs) that met our inclusion criteria. Overall, 1,764 women receiving intravenous tranexamic acid for prevention of bleeding following caesarean sections and 1,793 controls receiving placebo were enrolled in the 18 RCTs evaluated. The use of tranexamic acid compared to controls (placebo or no intervention) reduces post-partum haemorrhage >400 mL (risk ratio [RR] 0.40, 95% confidence interval [CI] 0.24-0.65; 5 trials with a total of 786 participants), severe post-partum haemorrhage >1,000 mL (RR 0.32, 95% CI: 0.12-0.84; 5 trials with a total of 1,850 participants), and need for red blood cell transfusion (RR 0.30, 95% CI: 0.18-0.49; 10 trials with a total of 1,873 participants). No particular safety concerns on the use of this antifibrinolytic agent emerged from the analysis of the 18 RCTs included. DISCUSSION Overall, the results of this meta-analysis support the evidence of a beneficial effect of tranexamic acid in reducing blood loss and need for blood transfusion in pregnant women undergoing caesarean section.