Abstract

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.

Abstract

BACKGROUND Postpartum haemorrhage (PPH) is a major cause of maternal morbidity and mortality worldwide. Tranexamic acid (TXA) is a useful drug for prevention of PPH and merits evaluation in Nigeria, where PPH is the leading cause of maternal death (25%) and severe maternal morbidity. This study evaluates the efficacy of TXA in reducing blood loss following vaginal delivery. METHODS This was a double-blind randomized placebo-controlled study on the efficacy and safety of intravenous TXA in reducing blood loss in women undergoing vaginal delivery in a tertiary hospital. Data analysis was conducted with IBM SPSS software (version 20, Chicago II, USA). P-value < 0.05 was considered statistically significant. RESULTS The mean estimated blood loss was lower in TXA compared with the placebo group. (174.87 ± 119.83 ml versus 341.07 ± 67.97 ml respectively; P < 0.0001). PPH (blood loss > 500 ml) was 5.13% in the study arm compared to the control arm 7.14%- risk ratio (RR) 0.71; 95% CI: 0.38-1.79, p = 0.5956]. Additional uterotonics was required more in the control group compared to the treatment group 14(16.67%) versus 3(3.85%), p-value= 0.007. There were no major complications noticed in the treatment group. CONCLUSION This study demonstrated that intravenous administration of TXA reduced blood loss following vaginal delivery. It also reduced the need for additional uterotonics. However, blood loss greater than 500 was not significantly reduced. TRIAL REGISTRATION This trial was registered retrospectively. Pan African Clinical Trial Registry: PACTR202010828881019 on 12/10/2020.

Abstract

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.

Abstract

Introduction Heavy menstrual bleeding (HMB) is characterized by high blood loss (>80 mL per cycle) at regular menstrual intervals. It can have an impact on a woman's bodily, mental, and/or material well-being. The etiology is varied and can be local, systemic, or iatrogenic. The occurrence of HMB is between 4% and 27%, depending on objective menstrual bleeding measurements and on high estimates based on subjective bleeding measures. This study was conducted to assess the efficacy of oral tranexamic acid versus combined oral contraceptive (COC) pills in the management of excessive menstrual bleeding. Methodology A comparative study was conducted at the Obstetrics and Gynecology Department of Combined Military Hospital Peshawar, Pakistan, from October 2020 to March 2021. Women aged above 18 years who presented with heavy menstrual bleeding (HMB) were included in the study. The exclusion criteria included all women with contraindications to the use of tranexamic acid, such as lactating mothers, pregnancy, use of oral contraceptives or steroids, history of renal malfunction or stroke, family history of thromboembolic disease, and ovarian or endometrial carcinoma. Patients with diagnosed leiomyomas with a size between >1 and 10 cm were included in the study. Women were allocated randomly into group A who received oral tranexamic acid 3.9-4 g per day or group B who received oral COC pills containing a combination of ethinyl estradiol 30 μg and norgestrel 0.3 mg. The efficacy of treatment was considered successful if there was a mean reduction in menstrual blood loss that was significantly greater than the baseline values. Results There were 178 patients in total, with 89 patients in each group. It was found that both oral tranexamic acid and combined oral contraceptives were equally effective in reducing the mean blood loss among patients and there was no statistical difference observed between the two groups. Upon stratification, it was found that both treatment groups were highly effective in younger age groups. Similarly, there was no significant difference in efficacy with respect to diabetes mellitus or hypertension. However, in individuals with leiomyomas, efficacy was significantly higher in patients who were in group B (combined oral contraceptives) (p = 0.004), and 46.1% of women in group A and 60.6% of women in group B did not experience any discomfort. Conclusion The current study revealed that both oral tranexamic acid and COC pills were equally effective in reducing the mean blood loss among patients with HMB. It was further found that the efficacy of both therapies was significantly higher in younger age groups. The efficacy of therapy was significantly reduced with the increasing age of the patient. Moreover, it was found that patients with leiomyomas benefitted more significantly from COC pills. There were no severe adverse effects reported in the study. However, future researches can explore the long-term side effects of both therapies. In short, both therapies were comparable in terms of efficacy and safety. Heavy menstrual bleeding can negatively impact a woman, emotionally and physically. Therefore, it is encouraged that physicians use their expert judgment while prescribing either oral tranexamic acid or COC pills to patients with HMB.

Abstract

INTRODUCTION Postpartum hemorrhage (PPH) is the most important concern after delivery. Tranexamic acid (TXA), an anti-fibrinolytic agent, has been suggested for prevention and treatment of PPH. OBJECTIVE The purpose of the present study was to find the effects of TXA on the amount of bleeding following vaginal delivery and its adverse effects. MATERIALS AND METHODS The study was performed as a randomized double blind placebo controlled clinical trial on low risk pregnant women who delivered vaginally. The patients were randomly assigned into two groups. Women in the intervention group received 10 mg/kg infusion of TXA in 100 mL normal saline and the control group received one vial of distilled water (as placebo) in 100 mL normal saline. The primary outcome was amount of bleeding after delivery. The secondary outcomes were decreased in hemoglobin level, need for additional uterotonic agents and need for blood transfusion. All were evaluated 6 h after delivery and compared in the two groups. Participants were followed up to six weeks after delivery for any TXA side effects. RESULTS Two hundred and seven women finished the study. There were no significant differences between the two groups in terms of demographic data and risk factors for bleeding. Mean blood loss and need to misoprostol was more in the control group (p=.033 and p=.000, respectively). Hemoglobin level was higher in the TXA group 6 h after delivery. None of the subjects needed blood transfusion, uterine balloon tamponade or emergency hysterectomy. Adverse effects were higher in the TXA group, however, there were no side effects between weeks 3 and 6 in both groups. There were no thromboembolic events during six weeks after delivery. CONCLUSIONS Tranexamic acid can reduce the amount of bleeding after vaginal delivery in low risk women without having serious complications. Also, it may decrease the need for additional uterotonic agents. Trial registration number and registry website: IRCT20091023002624N22.

Abstract

BACKGROUND Postpartum hemorrhage (PPH) is responsible for nearly one quarter of maternal deaths. A 2017 multicountry trial found that incorporating tranexamic acid (TXA) into the PPH management package was effective in reducing maternal death due to bleeding. OBJECTIVE To systematically review studies assessing the cost-effectiveness of tranexamic acid for PPH treatment. SEARCH STRATEGY Nine databases were searched using variations of keywords 'tranexamic acid', 'postpartum hemorrhage' and 'cost effectiveness'. SELECTION CRITERIA Eligible studies were any type of economic or effectiveness evaluation studies on tranexamic acid for treating women with PPH. DATA COLLECTION AND ANALYSIS Two reviewers independently screened citations and extracted data on cost effectiveness measures. Quality was assessed using the Consensus on Health Economic Criteria list. MAIN RESULTS Four studies were included, of which two were abstracts. Three studies concluded that early administration of TXA was cost-saving or cost-effective. One abstract reported TXA was not cost-effective in the USA unless the probability of death due to hemorrhage is higher. CONCLUSION Available evidence (four studies in three countries) suggests that this life-saving intervention may be below willingness to pay thresholds (cost-effective) or cost saving. Further studies conducted in different populations and settings are needed to inform health policy decision-making to reduce PPH-associated morbidity and mortality.

Abstract

BACKGROUND Oral tranexamic acid (TXA), if effective in reducing blood loss after delivery for women experiencing primary PPH, could be administered where parenteral administration is not feasible. This trial assessed the efficacy, safety, and acceptability of oral TXA when used as an adjunct to sublingual misoprostol to treat postpartum hemorrhage (PPH) following vaginal delivery. METHODS From October 2016 to January 2018, women presenting at four hospitals in Senegal and Vietnam for vaginal delivery were screened for enrollment in the trial. Women diagnosed with postpartum hemorrhage (defined as blood loss ≥700 ml) were randomized to receive either oral TXA (1950 mg) or placebo in addition to 800 mcg sublingual misoprostol. Postpartum blood loss was measured using a calibrated drape. Blood loss for all PPH cases was recorded for 2 h after administration of the drugs. The primary outcome measure was the proportion of women with bleeding controlled with the trial regimen without recourse to further treatment. Secondary outcomes including the rate of severe PPH, mean/median blood loss, use of additional uterotonics and/or interventions side effects, and acceptability were also recorded. RESULTS Of the 258 women who received treatment for PPH, 128 received placebo and misoprostol and 130 received TXA and misoprostol. The proportion of women who had active bleeding controlled with trial drugs alone and no additional interventions was similar in both groups: 77(60.2%) placebo; 74 (56.9%) TXA, p = 0.59). Use of other interventions to control bleeding, including uterotonics, did not differ significantly between groups. Median blood loss at PPH diagnosis was 700 ml in both groups. Uterine atony alone or in addition to another cause contributed to over 90% of PPH cases reported (92.2% placebo vs. 91.5% TXA), other causes included perineal and cervical lacerations and retained placenta. Reports of side effects and acceptability were similar in the two groups. CONCLUSION Adjunct use of oral TXA with misoprostol to treat PPH resulted in similar clinical and acceptability outcomes when compared to treatment with misoprostol alone. TRIAL REGISTRATION This trial was registered with ClinicalTrials.gov, number NCT02805426. Registered on 3 September 2016.

Abstract

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.

Abstract

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.

Abstract

OBJECTIVE To estimate the cost effectiveness of tranexamic acid (TXA) use to prevent postpartum hemorrhage. DESIGN A trial-based economic evaluation. SETTING 15 French university maternity hospitals. POPULATION women enrolled in the TRAAP randomized controlled trial comparing TXA versus placebo in women with vaginal delivery. TRAAP failed to show a reduction in postpartum hemorrhage of at least 500 ml in the intervention arm but evidenced significant lower rates of secondary outcomes related to blood loss METHODS & MAIN OUTCOME MEASURES We estimated direct medical costs from within-trial hospital resources collected prospectively from the study report form. All resources were costed at their value to the hospital. We estimated incremental cost per incremental hemorrhage averted. RESULTS Among the 4,079 women in the TRAAP trial, data necessary to calculate costs were available for 3,836 (94.0%). The average total costs in the TXA and control groups were €2,278 ±388 and €2,288 ±409 per woman respectively (p= 0.79). In women with postpartum hemorrhage of at least 500 ml (trial primary endpoint), costs were €2,359±354 and €2,409±525 (p=0.14); for provider-assessed clinically significant postpartum hemorrhage and postpartum hemorrhage of at least 1000 ml, costs were respectively €2,316±347 versus €2,381±521 (p=0.22) and €2,321±318versus €2,411±590 (p=0.35) in the tranexamic and placebo groups, respectively. The probabilistic sensitivity analysis showed that the use of TXA had a 65-73% % probability of being cost saving and outcome improving. CONCLUSIONS Our findings support the use of TXA as both bleeding events and cost may be reduced 3 out of 4 times.