Abstract

Postpartum haemorrhage (PPH) is a leading cause of maternal morbidity and mortality. While tranexamic acid (TXA) reduces bleeding and transfusion requirements in established PPH, we sought to determine the feasibility of conducting a fully powered trial assessing the effect of prophylactic tranexamic acid, prior to PPH onset, in a Canadian Obstetric setting. With institutional and Health Canada approval, consenting, eligible parturients (singleton, > 32 weeks gestation, vaginal or caesarian delivery) were randomly assigned to receive TXA (1 g intravenously) or placebo (0.9% saline) prior to delivery. Participants, investigators, data collectors/adjudicators, and analysis was blinded. The primary outcome was administration of study intervention to > 85% of randomized individuals. Secondary outcomes included recruitment rate (feasibility) and safety outcomes. Over 8 months, 611 were approached, 35 consented, and 27 randomized (14 TXA, 13 placebo). 89% of randomized participants received the assigned intervention. Recruitment fell below feasibility (23% target). No serious adverse outcomes occurred. Our pilot trial in a Canadian Obstetric setting was unable to demonstrate feasibility to conduct a large, multicentre trial to examine prophylactic use of tranexamic for PPH secondary to the complex regulatory requirements associated with a trial for an off-label, but commonly utilized intervention. These challenges should inform stakeholders on the resources and challenges of conducting future trials using off-label interventions.Trial registration: www.clinicaltrials.gov , NCT03069859 (03/03/2017).

Abstract

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).

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

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.

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

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.

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

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

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

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.