Antifibrinolytic drugs for treating primary postpartum haemorrhage.
Ontology highlight
ABSTRACT:
SUBMITTER: Shakur H
PROVIDER: S-EPMC6491317 | biostudies-literature | 2018 Feb
REPOSITORIES: biostudies-literature
Publications
Antifibrinolytic drugs for treating primary postpartum haemorrhage.
Shakur Haleema H Beaumont Danielle D Pavord Sue S Gayet-Ageron Angele A Ker Katharine K Mousa Hatem A HA
The Cochrane database of systematic reviews 20180220
<h4>Background</h4>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 ha ...[more]
Similar Datasets
Project description: Not available
| S-EPMC8407481 | biostudies-literature
Project description:BACKGROUND: Postpartum haemorrhage remains an important cause of maternal death despite treatment with conventional therapy. Uncontrolled studies and one randomised comparison with conventional oxytocics have reported dramatic effects with high-dose misoprostol, usually given rectally, for treatment of postpartum haemorrhage, but this has not been evaluated in a placebo-controlled trial. METHODS: The study was conducted at East London Hospital Complex, Tembisa and Chris Hani Baragwanath Hospitals, South Africa. Routine active management of the third stage of labour was practised. Women with more than usual postpartum bleeding thought to be related to inadequate uterine contraction were invited to participate, and to sign informed consent. All routine treatment was given from a special 'Postpartum Haemorrhage Trolley'. In addition, participants who consented were enrolled by drawing the next in a series of randomised treatment packs containing either misoprostol 5 x 200 microg or similar placebo, which were given 1 orally, 2 sublingually and 2 rectally. RESULTS: With misoprostol there was a trend to reduced blood loss >/=500 ml in 1 hour after enrolment measured in a flat plastic 'fracture bedpan', the primary outcome (6/117 vs 11/120, relative risk 0.56; 95% confidence interval 0.21 to 1.46). There was no difference in mean blood loss or haemoglobin level on day 1 after birth < 6 g/dl or blood transfusion. Side-effects were increased, namely shivering (63/116 vs 30/118; 2.14, 1.50 to 3.04) and pyrexia > 38.5 degrees C (11/114 vs 2/118; 5.69, 1.29 to 25). In the misoprostol group 3 women underwent hysterectomy of whom 1 died, and there were 2 further maternal deaths. CONCLUSIONS: Because of a lower than expected incidence of the primary outcome in the placebo group, the study was underpowered. We could not confirm the dramatic effect of misoprostol reported in several unblinded studies, but the results do not exclude a clinically important effect. Larger studies are needed to assess substantive outcomes and risks before misoprostol enters routine use.
| S-EPMC514549 | biostudies-literature
Project description:BackgroundEach year, worldwide about 530,000 women die from causes related to pregnancy and childbirth. Of the deaths 99% are in low and middle income countries. Obstetric haemorrhage is the leading cause of maternal mortality, most occurring in the postpartum period. Systemic antifibrinolytic agents are widely used in surgery to prevent clot breakdown (fibrinolysis) in order to reduce surgical blood loss. At present there is little reliable evidence from randomised trials on the effectiveness of tranexamic acid in the treatment of postpartum haemorrhage.MethodsThe Trial aims to determine the effect of early administration of tranexamic acid on mortality, hysterectomy and other morbidities (surgical interventions, blood transfusion, risk of non-fatal vascular events) in women with clinically diagnosed postpartum haemorrhage. The use of health services and safety, especially thromboembolic effect, on breastfed babies will also be assessed. The trial will be a large, pragmatic, randomised, double blind, placebo controlled trial among 15,000 women with a clinical diagnosis of postpartum haemorrhage. All legally adult women with clinically diagnosed postpartum haemorrhage following vaginal delivery of a baby or caesarean section will potentially be eligible. The fundamental eligibility criterion is the responsible clinician's 'uncertainty' as to whether or not to use an antifibrinolytic agent in a particular woman with postpartum haemorrhage. Treatment will entail a dose of tranexamic acid (1 gram by intravenous injection) or placebo (sodium chloride 0.9%) will be given as soon as possible after randomisation. A second dose may be given if after 30 minutes bleeding continues, or if it stops and restarts within 24 hours after the first dose. The main analyses will be on an 'intention to treat' basis, irrespective of whether the allocated treatment was received or not. Subgroup analyses for the primary outcome will be based on type of delivery; administration or not of prophylactic uterotonics; and on whether the clinical decision to consider trial entry was based primarily on estimated blood loss alone or on haemodynamic instability. A study with 15,000 women will have over 90% power to detect a 25% reduction from 4% to 3% in the primary endpoint of mortality or hysterectomy.
| S-EPMC2864262 | biostudies-literature
Project description:Fibrinolysis is a natural process that ensures blood fluidity through the removal of fibrin deposits. However, excessive fibrinolytic activity can lead to complications in different circumstances, such as general surgery or severe trauma. The current antifibrinolytic drugs in the market, aminocaproic acid (EACA) and tranexamic acid (TXA), require high doses repetitively to maintain their therapeutic effect. These high doses are related to a number of side effects such as headaches, nasal symptoms, or gastrointestinal discomfort and severely limit their use in patients with renal impairment. Therefore, the discovery of novel antifibrinolytics with a higher specificity and lower dosage could vastly improve the applicability of these drugs. Herein, we synthesized a total of ten compounds consisting of a combination of three key moieties: an oxadiazolone, a triazole, and a terminal amine. The IC50 of each compound was calculated in our clot lysis assays, and the best candidate (1) provided approximately a 2.5-fold improvement over the current gold standard, TXA. Molecular docking and molecular dynamics were used to perform a structure-activity relationship (SAR) analysis with the lysine binding site in the Kringle 1 domain of plasminogen. This analysis revealed that 1,2,3-triazole was crucial for the activity, enhancing the binding affinity through pi-pi stacking and polar interactions with Tyr72. The results presented in this work open the door to further investigate this new family as potential antifibrinolytic drugs.
| S-EPMC9736318 | biostudies-literature
Project description:BackgroundPostpartum haemorrhage (PPH) is an obstetric emergency. While PPH-related deaths are relatively rare in high-resource settings, PPH continues to be the leading cause of maternal mortality in limited-resource settings. We undertook a systematic review to identify, assess, and synthesise cost-effectiveness evidence on postpartum interventions to prevent, diagnose, or treat PPH.Methods and findingsThis systematic review was prospectively registered on PROSPERO (CRD42023438424). We searched Medline, Embase, NHS Economic Evaluation Database (NHS EED), EconLit, CINAHL, Emcare, Web of Science, and Global Index Medicus between 22 June 2023 and 11 July 2024 with no date or language limitations. Full economic evaluations of any postpartum intervention for prevention, detection, or management of PPH were eligible. Study screening, data extraction, and quality assessments (using the CHEC-E tool) were undertaken independently by at least 2 reviewers. We developed narrative syntheses of available evidence for each intervention. From 3,993 citations, 56 studies were included: 33 studies of preventative interventions, 1 study assessed a diagnostic method, 17 studies of treatment interventions, 1 study comparing prevention and treatment, and 4 studies assessed care bundles. Twenty-four studies were conducted in high-income countries, 22 in upper or lower middle-income countries, 3 in low-income countries, and 7 studies involved countries of multiple income levels. Study settings, methods, and findings varied considerably. Interventions with the most consistent findings were the use of tranexamic acid for PPH treatment and using care bundles. In both cases, multiple studies predicted these interventions would either result in better health outcomes and cost savings, or better health outcomes at acceptable costs. Limitations for this review include that no ideal setting was chosen, and therefore, a transferability assessment was not undertaken. In addition, some sources of study uncertainty, such as effectiveness parameters, were interrogated to a greater degree than other sources of uncertainty.ConclusionsIn this systematic review, we extracted, critically appraised, and summarised the cost-effectiveness evidence from 56 studies across 16 different interventions for the prevention, diagnosis, and treatment of PPH. Both the use of tranexamic acid as part of PPH treatment, and the use of comprehensive PPH bundles for prevention, diagnosis, and treatment have supportive cost-effectiveness evidence across a range of settings. More studies utilizing best practice principles are required to make stronger conclusions on which interventions provide the best value. Several high-priority interventions recommended by World Health Organization (WHO) such as administering additional uterotonics, non-pneumatic anti-shock garment, or uterine balloon tamponade (UBT) for PPH management require robust economic evaluations across high-, middle-, and low-resource settings.
| S-EPMC11433145 | biostudies-literature
Project description:In Gabon, the proportion of maternal deaths directly related to Primary PostPartum Haemorrhage (PPPH) is 15 to 25%, despite the different means that the World Health Organization has made available to the providers of Emergency Obstetrical and Neonatal Care (EmONC). The objective of this study was to determine the prevalence and epidemiological characteristics of Primary PostPartum Haemorrhage to improve its management and reduce the rate of maternal deaths. An analytical retrospective study involved 42,728 records, whose data were collected using a chart collection form on the basis of information contained in partograms and other patient records. Sociodemographic variables were expressed using percentage. The relationship between the etiologies of PPPH and certain characteristics of the women was established using the ORs with their 95% confidence intervals. The difference was significant if p < 0.05. The prevalence of PPPH was 1.6%. Delivery haemorrhages accounted for 65.5% of PPPH. The main factors associated with delivery haemorrhages were pauci parity and multiparity (p = 0.003 and 0.051), post-term (p = 0.042), and birth weight >4,000 g (p = 0.006). Those associated with genital tract injuries were young maternal age (p = 0.008) and multiparity (p = 0.028). The most common etiology was haemorrhage from delivery. Multiparity remains the most common risk factor and the young age of the patients. It is important to improve management through better assessment of blood loss in the primary postpartum period as well as capacity building of health providers on EmONC.
| S-EPMC8452036 | biostudies-literature
Project description:ObjectivesTo explore the association between postpartum haemorrhage (PPH) and postpartum depression (PPD), taking into account the role of postpartum anaemia, delivery experience and psychiatric history.MethodsA nested cohort study (n = 446), based on two population-based cohorts in Uppsala, Sweden. Exposed individuals were defined as having a bleeding of ≥1000 ml (n = 196) at delivery, and non-exposed individuals as having bleeding of <650 ml (n = 250). Logistic regression models with PPD symptoms (Edinburgh Postnatal Depression scale (EPDS) score ≥ 12) as the outcome variable and PPH, anaemia, experience of delivery, mood during pregnancy and other confounders as exposure variables were undertaken. Path analysis using Structural Equation Modeling was also conducted.ResultsThere was no association between PPH and PPD symptoms. A positive association was shown between anaemia at discharge from the maternity ward and the development of PPD symptoms, even after controlling for plausible confounders (OR = 2.29, 95%CI = 1.15-4.58). Path analysis revealed significant roles for anaemia at discharge, negative self-reported delivery experience, depressed mood during pregnancy and postpartum stressors in increasing the risk for PPD.ConclusionThis study proposes important roles for postpartum anaemia, negative experience of delivery and mood during pregnancy in explaining the development of depressive symptoms after PPH.
| S-EPMC4726585 | biostudies-literature
Project description:BackgroundTo determine the prevalence, related factors and maternal outcomes of primary PPH in governmental hospitals in Kabul Afghanistan.MethodsAn observational study was designed to determine the prevalence, related factors and maternal outcomes of primary PPH in governmental hospitals in Kabul-Afghanistan. The population of this study consisted of all women who gave birth to a child between August and October 2018. The structured checklist was used to collect the data from patients who were suffering from primary PPH.ResultsAmong the 8652 women who were observed, 215 (2.5%) of them suffered from primary PPH and 2 (0.9%) of them died under caesarean section. The most common related factors of primary PPH were uterine atonia (65.6%), previous PPH (34.9%), prolonged labor (27%), genital tract trauma (26.5%), and induction of labor (20.5%). The most common maternal outcomes of primary PPH were respiratory failure (7%), hysterectomy (6%), and hypovolaemic shock (5.1%).ConclusionsAccording to our findings, the major cause of postpartum bleeding was uterine atonia. Therefore, postpartum care of women is essential, especially for those with previous PPH and prolonged labor that require more attention.
| S-EPMC7390104 | biostudies-literature
Project description:BackgroundOf the 1010 reported maternal deaths in 2018, just over 65% occurred in hospitals in Ethiopia. However, there is a lack of standardised data about the contributing factors. This study aimed to investigate the incidence, mortality, and factors associated with primary postpartum haemorrhage following in-hospital births in northwest Ethiopia.MethodsA retrospective cohort design was used; an audit of 1060 maternity care logbooks of adult women post-partum at Felege Hiwot Referral Hospital and University of Gondar Comprehensive Specialized Hospital. The data were abstracted between December 2018 and May 2019 using a systematic random sampling technique. We used the Facility Based Maternal Death Abstraction Form containing sociodemographic characteristics, women's medical history, and partographs. Primary postpartum haemorrhage was defined as the estimated blood loss recorded by the staff greater or equal to 500 ml for vaginal births and 1000 ml for caesarean section births, or the medical doctor diagnosis and recording of the woman as having primary postpartum haemorrhage. The data analysis was undertaken using Stata version 15. Variables with P ≤ 0.10 for significance were selected to run multivariable logistic analyses. Variables that had associations with primary postpartum haemorrhage were identified based on the odds ratio, with 95% confidence interval (CI) and P-value less than 0.05.ResultsThe incidence of primary postpartum haemorrhage in the hospitals was 8.8% (95% CI: 7.2, 10.6). Of these, there were 7.4% (95% CI: 2.1, 13.3) maternal deaths. Eight predictor variables were found to be independently associated with primary postpartum haemorrhage, including age ≥35 years (AOR: 2.20; 95% CI: 1.08, 4.46; P = 0.03), longer than 24 hours duration of labour (AOR: 7.18; 95% CI: 2.73, 18.90; P = 0.01), vaginal or cervical lacerations (AOR: 4.95; 95% CI: 2.49, 9.86; P = 0.01), instrumental (forceps or vacuum)-assisted birth (AOR: 2.92; 95% CI: 1.25, 6.81; P = 0.01), retained placenta (AOR: 21.83; 95% CI: 6.33, 75.20; P = 0.01), antepartum haemorrhage in recent pregnancy (AOR: 6.90; 95% CI: 3.43, 13. 84; p = 0.01), women in labour referred from primary health centres (AOR: 2.48; 95% CI: 1.39, 4.42; P = 0.02), and births managed by medical interns (AOR: 2.90; 95% CI: 1.55, 5.37; P = 0.01).ConclusionWe found that while the incidence of primary postpartum haemorrhage appeared to be lower than in other studies in Africa the associated maternal mortality was higher. Although most factors associated with primary postpartum haemorrhage were consistent with those identified in the literature, two additional specific factors, were found to be prevalent among women in Ethiopia; the factors were referred women in labour from primary health facilities and births managed by medical interns. Maternal healthcare providers in these hospitals require training on the management of a birthing emergency.
| S-EPMC8986012 | biostudies-literature
Project description:ObjectiveTo assess whether secondary prevention, which preemptively treats women with above-average postpartum bleeding, is non-inferior to universal prophylaxis.DesignA cluster-randomised non-inferiority community trial.SettingHealth sub-centres and home deliveries in the Bijapur district of Karnataka, India.PopulationWomen with low-risk pregnancies who were eligible for delivery with an Auxiliary Nurse Midwife at home or sub-centre and who consented to be part of the study.MethodsAuxiliary Nurse Midwifes were randomised to secondary prevention using 800 mcg sublingual misoprostol administered to women with postpartum blood loss ≥350 ml or to universal prophylaxis using 600 mcg oral misoprostol administered to all women during the third stage of labour.Main outcome measuresPostpartum haemoglobin ≤7.8 g/dl, mean postpartum blood loss and postpartum haemoglobin, postpartum haemorrhage rate, transfer to higher-level facilities, acceptability and feasibility of the intervention.ResultsMisoprostol was administered to 99.7% of women as primary prevention. In secondary prevention, 92 (4.7%) women had postpartum bleeding ≥350 ml, of which 90 (97.8%) received misoprostol. The proportion of women with postpartum haemoglobin ≤7.8 g/dl was 5.9 and 8.8% in secondary and primary prevention clusters, respectively [difference -2.9%, one-sided 95% confidence interval (CI) <1.3%]. Postpartum transfer and haemorrhage rates were low (<1%) in both groups. Shivering was more common in primary prevention clusters (P = 0.013).ConclusionSecondary prevention of postpartum haemorrhage with misoprostol is non-inferior to universal prophylaxis based on the primary outcome of postpartum haemoglobin. Secondary prevention could be a good alternative to universal prophylaxis as it medicates fewer women and is an acceptable and feasible strategy at the community level.Tweetable abstractSecondary prevention of postpartum haemorrhage with misoprostol is non-inferior to universal prophylaxis.
| S-EPMC5014137 | biostudies-literature