Low-dose aspirin for the prevention of preterm birth in nulliparous women: systematic review and meta-analysis.

OBJECTIVE: The objective was to assess the efficacy and safety of low-dose aspirin for the prevention of preterm birth in nulliparous women. DATA SOURCES: We searched PubMed, Embase and the Cochrane Central Register of Controlled Trials (CENTRAL) from inception to June 2022. STUDY ELIGIBILITY CRITERIA: Randomized controlled trials that compared aspirin to placebo in nulliparous women were eligible. METHODS: This study was reported in accordance with the PRISMA 2020 checklist. The primary outcomes of this study were the rates of preterm birth at less than 37 weeks and less than 34 weeks of gestation. The secondary outcomes included postpartum hemorrhage, placental abruption, cesarean section, any hypertensive disorder of pregnancy and small for gestational age. Relative risks with their 95% confidence intervals were calculated for analysis. Heterogeneity was assessed by Cochran's Q test and Higgins's I2. A random-effects model was used when I2 was > 50% to generate the RR and 95% CI; otherwise, a fixed-effects model was used. The risk of publication bias was assessed by funnel plots. We performed sensitivity analysis by sequentially omitting each included study to confirm the robustness of the analysis. RESULTS: Seven studies with a total of 29,029 participants were included in this review. Six studies were assessed as having a low risk of bias or an unclear risk of bias, and one study was judged as having a high risk of bias. In nulliparous women, low-dose aspirin was associated with a significant reduction in the rate of preterm birth at less than 34 weeks of gestational age (RR 0.84,95% CI: 0.71-0.99; I2 = 0%; P = 0.04), but we did not observe a significant difference in the rate of preterm birth at less than 37 weeks of gestation (RR 0.96,95% CI: 0.90-1.02; I2 = 31%; P = 0.18). Low-dose aspirin was associated with a significant increase in the rates of postpartum hemorrhage (RR 1.32,95% CI: 1.14-1.54; I2 = 0%; P = 0.0003), placental abruption (RR 2.18,95% CI: 1.10-4.32; I2 = 16%; P = 0.02) and cesarean section (RR 1.053, 95% CI: 1.001-1.108; I2 = 0%; P = 0.05) in nulliparous women. We also did not observe a significant effect of low-dose aspirin on the rates of any hypertensive disorder of pregnancy (RR 1.05, 95% CI: 0.96-1.14; I2 = 9%; P = 0.28) or small for gestational age (RR 0.96, 95% CI: 0.91-1.02; I2 = 0%; P = 0.16) in nulliparous women. Funnel plots indicated that no significant publication bias existed in this meta-analysis. Except for preterm birth at less than 34 weeks of gestation, placental abruption and cesarean section, the sensitivity analysis showed similar results, which confirmed the robustness of this meta-analysis. CONCLUSIONS: Low-dose aspirin might reduce the risk of preterm birth at less than 34 weeks of gestation in nulliparous women. The use of low-dose aspirin in nulliparous women increased the risk of postpartum hemorrhage and might increase the risk of placental abruption and cesarean section.

Role of recombinant factor VIIa in the clinical management of severe postpartum hemorrhage: consensus among European experts.

OBJECTIVES: There have been significant advances in the medical management of severe postpartum hemorrhage (sPPH) over recent decades, which is reflected in numerous published guidelines. To date, many of the currently available national and international guidelines recommend recombinant factor VIIa (rFVIIa) to be used only at a very late stage in the course of sPPH, as a "last resort", before or after hysterectomy. Based on new safety data, rFVIIa has recently been approved by the European Medicines Agency (EMA) and Swissmedic for use in sPPH, if uterotonics are insufficient to achieve hemostasis, which in fact is significantly earlier in the course of postpartum hemorrhage (PPH). We therefore aimed to develop expert consensus guidance as a step toward standardizing care with the use of rFVIIa for clinicians managing women experiencing life-threatening sPPH. METHODS: The consensus process consisted of one face-to-face meeting with a group of nine experts, including eight obstetrician-gynecologists and a hematologist highly experienced in sPPH care in tertiary care perinatal centers. The panel was representative of multidisciplinary expertise in the European obstetrics community and provided consensus opinion in answer to pre-defined questions around clinical practice with rFVIIa in the management of sPPH. Recommendations have been based on current national and international guidelines, extensive clinical experience, and consensus opinion, as well as the availability of efficacy and new safety data. RESULTS: The expert panel developed 17 consensus statements in response to the 13 pre-defined questions on the use of rFVIIa in the management of sPPH including: available efficacy and safety data and the need for interdisciplinary expertise between obstetricians, anesthesiologists, and hematologists in the management of sPPH. Based on novel data, the experts recommend: (1) earlier administration of rFVIIa in patients with sPPH who do not respond to uterotonic administration to optimize the efficacy of rFVIIa; (2) the importance of hematological parameter prerequisites prior to the administration of rFVIIa to maximize efficacy; and (3) continued evaluation or initiation of further invasive procedures according to standard practice. Furthermore, recommendations on the timing of rFVIIa treatment within the sPPH management algorithm are outlined in a range of specified clinical scenarios and settings, including vaginal delivery, cesarean section, and smaller birthing units before transfer to a tertiary care center. The panel agreed that according to available, and new data, as well as real-world experience, there is no evidence that the use of rFVIIa in patients with sPPH increases the risk of thromboembolism. The authors acknowledge that there is still limited clinical effectiveness data, as well as pharmacoeconomic data, on the use of rFVIIa in sPPH, and recommend further clinical trials and efficacy investigation. CONCLUSIONS: This expert panel provides consensus guidance based on recently available data, clinical experience, and expert opinion, augmented by the recent approval of rFVIIa for use in sPPH by the EMA. These consensus statements are intended to support clinical care for sPPH and may help to provide the impetus and a starting point for updates to existing clinical practice guidelines.

Animal models of postpartum hemorrhage.

Postpartum hemorrhage (PPH)-heavy bleeding following childbirth-is a leading cause of morbidity and mortality worldwide. PPH can affect individuals regardless of risks factors and its incidence has been increasing in high-income countries including the United States. The high incidence and severity of this childbirth complication has propelled research into advanced treatments and alternative solutions for patients facing PPH; however, the development of novel treatments is limited by the absence of a common, well-established and well-validated animal model of PPH. A variety of animals have been used for in vivo studies of novel therapeutic materials; however, each of these animals differs considerably from the anatomy and physiology of a postpartum woman, and the methods used for achieving a postpartum hemorrhagic condition vary widely. Here we critically evaluate the various animal models of PPH presented in the literature and propose additional and alternative methods for modeling PPH in in vivo studies. We highlight how current animal models successfully or unsuccessfully mimic the anatomy and physiology of a postpartum woman and how this may impact treatment development. We aim to equip researchers with the necessary background information to select appropriate animal models for their research related to PPH solutions, while supporting the goals of refinement, reduction and replacement (3Rs) in preclinical animal studies.

Tranexamic acid versus oxytocin for primary postpartum Haemorrhage in the out-of-hospital setting: A systematic review with implications for rural practice.

INTRODUCTION: Primary postpartum haemorrhage causes approximately 25% of global maternal deaths and accounts for significant maternal morbidity. While high certainty evidence demonstrates that tranexamic acid reduces comparative blood loss in postpartum haemorrhage in hospital settings, limited data exist on the specific pharmacological management of this condition in out-of-hospital settings, and the implications for rural communities. OBJECTIVE: To determine the efficacy of oxytocin compared to tranexamic acid in women suffering postpartum haemorrhage in the out-of-hospital environment. DESIGN: A systematic review comparing evidence containing patients with postpartum haemorrhage in the out-of-hospital and/or rural setting, in which oxytocin/tranexamic acid were used. Outcome measures were comparative blood loss/haemorrhagic shock, the need for further interventions and maternal/neonatal morbidity/mortality. FINDINGS: No randomised control trials have been conducted in an out-of-hospital environment in relation to oxytocin/tranexamic acid. In this setting, there is no difference in outcome measures when using oxytocin compared to no intervention, or oxytocin compared to standard care. Data are lacking on the effect of tranexamic acid on the same outcome measures. DISCUSSION: Rural and out-of-hospital management of postpartum haemorrhage is limited by resource availability and practitioner availability, capacity and experience. In-hospital evidence may lack transferability, therefore direct evidence on the efficacy of pharmacological management in these contexts is scant and requires redress. CONCLUSION: There is no difference in blood loss, neonatal or maternal mortality or morbidity, or need for further interventions, when using oxytocin or TXA compared to no intervention, or compared to standard care, for PPH. Further studies are needed on the efficacy of these drugs, and alternate or co-drug therapies, for PPH in the out-of-hospital environment and rural clinical practice.

Preventing postpartum hemorrhage: A network meta-analysis on routes of administration of uterotonics.

1. OBJECTIVE: To perform a network meta-analysis to specify the route of administration that maximises the effectiveness of each of the available prophylactic uterotonics without increasing the risk for side effects. 2. DATA SOURCES: Literature searches on 12th September 2022 included: CENTRAL, MEDLINE, Embase, CINAHL, ClinicalTrials.gov and the WHO International Clinical Trials Registry Platform. The reference lists of the retrieved study records were also searched. 3. STUDY ELIGIBILITY CRITERIA: Population: Randomized controlled trials involving women in the third stage of labour after a vaginal or caesarean delivery in hospital or community settings. INTERVENTIONS: Systemically administered prophylactic uterotonics of any route and dose for primary postpartum hemorrhage prevention. Comparison: Any other prophylactic uterotonic, or a different route or dose of a given uterotonic, or placebo, or no treatment. Outcomes (primary): postpartum hemorrhage ≥ 500 mL and ≥ 1000 mL. 4. STUDY APPRAISAL AND SYNTHESIS METHODS: Risk of bias and trustworthiness assessments were performed, according to Cochrane's guidance. Direct, indirect and network meta-analyses were conducted, and results were summarized either as risk ratio or mean difference with 95% confidence intervals for dichotomous and continuous outcomes, respectively. The certainty of generated evidence was assessed according to the GRADE approach. Cumulative probabilities were calculated and the surface under the cumulative ranking curve was used to create a ranking of the available drugs. 5. RESULTS: One hundred eighty-one studies involving 122,867 randomised women were included. Most studies were conducted in hospital settings in lower-middle income countries and involved women delivering vaginally. When compared with intramuscular oxytocin, carbetocin (RR 0.58, 95 % CI 0.40-0.84) and oxytocin (RR 0.75, 95 % CI 0.59-0.97) by an intravenous bolus, and intramuscular ergometrine plus oxytocin combination (RR 0.71, 95 % CI 0.56-0.91) are probably more effective in preventing primary postpartum hemorrhage. Intramuscularly administered oxytocin and carbetocin by an intravenous bolus have a favourable side effects profile. 6. CONCLUSIONS: Generated evidence was generally moderate and global inconsistency was low. Carbetocin and oxytocin by an intravenous bolus, and intramuscular ergometrine plus oxytocin combination are probably the top uterotonics for primary postpartum hemorrhage prevention. Large scale studies exploring different routes of administration for available prophylactic uterotonics, and women's views should be conducted.

Evaluating tranexamic acid for the prevention and treatment of obstetric hemorrhage.

PURPOSE OF REVIEW: Tranexamic acid (TXA) has emerged as a promising pharmacological adjunct to treat and prevent postpartum hemorrhage (PPH). We provide an overview of TXA, including its pharmacology, key findings of randomized trials and observational studies, and critical patient safety information. RECENT FINDINGS: Pharmacokinetic data indicate that TXA infusions result in peak plasma concentration within 3 min (range: 1-6.6 min). Ex-vivo pharmacodynamic data suggest that low-dose TXA (5 mg/kg) inhibits maximum lysis for at least 1 h. In predominantly developing countries, TXA has demonstrated a 19% reduction in the risk of bleeding-related death among patients with PPH. Based on high-quality randomized trials, TXA prophylaxis does not effectively reduce the risk of PPH during vaginal delivery and is likely ineffective in reducing the PPH risk during cesarean delivery. TXA exposure does not increase the risk of maternal thrombotic events. Maternal deaths have occurred from accidental intrathecal TXA injection from look-alike medication errors. SUMMARY: TXA has shown promise as an important adjunct for PPH treatment, especially in low-resource settings. However, TXA is not recommended as PPH prophylaxis during vaginal or cesarean delivery. Patient safety initiatives should be prioritized to prevent maternal death from accidental intrathecal TXA injection.

Effect of esketamine on postpartum depression after labor analgesia and potential mechanisms: a randomized, double-blinded controlled trial.

BACKGROUND: To evaluate the effect of esketamine combined with ropivacaine hydrochloride on the occurrence of postpartum depression (PPD) after labor analgesia under epidural analgesia pump and explore the possible mechanisms. METHODS: A total of 120 women aged 24 to 36 years old who underwent labor analgesia by epidural analgesia pump, with American Society of Anesthesiologists (ASA) physical status II were enrolled. According to the formula of epidural analgesia pump, all participants were randomly divided into two groups: esketamine group (Group E) and control group (Group C). Epidural anaesthesia were operated in all women between L2 and L3 after cervical dilation up to 2 ~ 3 cm. After successful puncture, the epidural catheter was placed 3.5 cm toward the head and 1% lidocaine was injected for 3 ml. The epidural analgesia pump was connected. Esketamine (0.2 mg/kg) combined with 0.75% ropivacaine hydrochloride (20 ml) were diluted by normal saline up to 100 ml in Group E, when only the equal dose of ropivacaine hydrochloride was used in Group C. The visual analogue scale (VAS) before analgesia (T1), 5 (T2), 10 (T3) and 20 (T4) minutes after analgesia were measured. The duration of the first and second stage of labor, the Apgar score of fetus at delivery, postpartum hemorrhage, consumption of esketamine and ropivacaine were recorded. The incidence of PPD was recorded at 1 week and 6 weeks after delivering. The occurrence of side effects such as nausea and vomiting, dizziness, and nightmares were also recorded for 48 h after delivering. The levels of leptin, norepinephrine(NE), and epinephrine(E) in the peripheral venous blood were measured before labor analgesia and at 24 h, 1 week, and 6 weeks after delivering. RESULTS: Compared with Group C, the VAS score at T2, T3 and T4 were significantly lower in Group E (P < 0.01). Compared with Group C, the incidence of PPD was significantly lower at 1 week and 6 weeks after delivering in Group E (P < 0.01). Compared with Group C, the levels of leptin were significantly higher at 24 h and 1 week after delivering in Group E (P < 0.01), while NE and E (P < 0.01) were lower at the same time (P < 0.01). There were no significant difference of the duration of the first and second stage of labor, the Apgar score of fetus at delivery, postpartum hemorrhage, consumption of ropivacaine and the side effects for 48 h after delivering between the two groups. CONCLUSION: Esketamine combined with ropivacaine hydrochloride used in labor analgesia can significantly reduce the incidence of postpartum depression after delivering without increasing related side effects, which may be related to the regulation of leptin, norepinephrine, and epinephrine in the serum. TRIAL REGISTRATION: The trial was registered at the Chinese Clinical Trial Registry on 30/05/2022 (CTRI registration number-ChiCTR2200060387). URL of registry: https://www.chictr.org.cn/bin/home .

Clinical chorioamnionitis at term: definition, pathogenesis, microbiology, diagnosis, and treatment.

Clinical chorioamnionitis, the most common infection-related diagnosis in labor and delivery units, is an antecedent of puerperal infection and neonatal sepsis. The condition is suspected when intrapartum fever is associated with two other maternal and fetal signs of local or systemic inflammation (eg, maternal tachycardia, uterine tenderness, maternal leukocytosis, malodorous vaginal discharge or amniotic fluid, and fetal tachycardia). Clinical chorioamnionitis is a syndrome caused by intraamniotic infection, sterile intraamniotic inflammation (inflammation without bacteria), or systemic maternal inflammation induced by epidural analgesia. In cases of uncertainty, a definitive diagnosis can be made by analyzing amniotic fluid with methods to detect bacteria (Gram stain, culture, or microbial nucleic acid) and inflammation (white blood cell count, glucose concentration, interleukin-6, interleukin-8, matrix metalloproteinase-8). The most common microorganisms are Ureaplasma species, and polymicrobial infections occur in 70% of cases. The fetal attack rate is low, and the rate of positive neonatal blood cultures ranges between 0.2% and 4%. Intrapartum antibiotic administration is the standard treatment to reduce neonatal sepsis. Treatment with ampicillin and gentamicin have been recommended by professional societies, although other antibiotic regimens, eg, cephalosporins, have been used. Given the importance of Ureaplasma species as a cause of intraamniotic infection, consideration needs to be given to the administration of antimicrobial agents effective against these microorganisms such as azithromycin or clarithromycin. We have used the combination of ceftriaxone, clarithromycin, and metronidazole, which has been shown to eradicate intraamniotic infection with microbiologic studies. Routine testing of neonates born to affected mothers for genital mycoplasmas could improve the detection of neonatal sepsis. Clinical chorioamnionitis is associated with decreased uterine activity, failure to progress in labor, and postpartum hemorrhage; however, clinical chorioamnionitis by itself is not an indication for cesarean delivery. Oxytocin is often administered for labor augmentation, and it is prudent to have uterotonic agents at hand to manage postpartum hemorrhage. Infants born to mothers with clinical chorioamnionitis near term are at risk for early-onset neonatal sepsis and for long-term disability such as cerebral palsy. A frontier is the noninvasive assessment of amniotic fluid to diagnose intraamniotic inflammation with a transcervical amniotic fluid collector and a rapid bedside test for IL-8 for patients with ruptured membranes. This approach promises to improve diagnostic accuracy and to provide a basis for antimicrobial administration.

Prophylactic tranexamic acid for reducing intraoperative blood loss during cesarean section in women at high risk of postpartum hemorrhage: A double-blind placebo randomized controlled trial.

BACKGROUND: Postpartum hemorrhage remains a leading cause of maternal mortality especially in developing countries. The majority of previous trials on the effectiveness of tranexamic acid in reducing blood loss were performed in low-risk women for postpartum hemorrhage. A recent Cochrane Systematic Review recommended that further research was needed to determine the effects of prophylactic tranexamic acid for preventing intraoperative blood loss in women at high risk of postpartum hemorrhage. OBJECTIVE: This study aimed to evaluate the effectiveness and safety of tranexamic acid in reducing intraoperative blood loss when given prior to cesarean delivery in women at high risk of postpartum hemorrhage. STUDY DESIGN: The study is a double-blind randomized controlled trial. METHODS: The study consisted of 200 term pregnant women and high-risk preterm pregnancies scheduled for lower-segment cesarean delivery at Enugu State University of Science and Technology, Teaching Hospital, Parklane, Enugu, Nigeria. The participants were randomized into two arms (intravenous 1 g of tranexamic acid or placebo) in a ratio of 1:1. The participants received either 1 g of tranexamic acid or placebo (20 mL of normal saline) intravenously at least 10 min prior to commencement of the surgery. The primary outcome measures were the mean intraoperative blood loss and hematocrit change 48 h postoperatively. RESULTS: The baseline sociodemographic characteristics were similar in both groups. The tranexamic acid group when compared to the placebo group showed significantly lower mean blood loss (442.94 ± 200.97 versus 801.28 ± 258.68 mL; p = 0.001), higher mean postoperative hemoglobin (10.39 + 0.96 versus 9.67 ± 0.86 g/dL; p = 0.001), lower incidence of postpartum hemorrhage (1.0% versus 19.0%; p = 0.001), and lower need for use of additional uterotonic agents after routine management of the third stage of labor (39.0% versus 68.0%; p = 0.001), respectively. However, there was no significant difference in the mean preoperative hemoglobin (11.24 ± 0.88 versus 11.15 ± 0.90 g/dL; p = 0.457), need for other surgical intervention for postpartum hemorrhage (p > 0.05), and reported side effect, respectively, between the two groups. CONCLUSION: Prophylactic administration of tranexamic acid significantly decreases postpartum blood loss, improves postpartum hemoglobin, decreases the need for additional uterotonics, and prevents postpartum hemorrhage following cesarean section in pregnant women at high risk of postpartum hemorrhage. Its routine use during cesarean section in high-risk women may be encouraged.The trial was registered in the Pan-African Clinical Trial Registry with approval number PACTR202107872851363.

Awareness and use of tranexamic acid in the management of postpartum hemorrhage among health care professionals in Enugu, Nigeria.

OBJECTIVES: This study was conducted to determine the knowledge, practice, and barriers regarding the use of tranexamic acid (TXA) for the prevention and treatment of postpartum hemorrhage (PPH) among health care providers in Enugu, Nigeria. METHODS: A cross-sectional study was conducted among health professionals (doctors, pharmacists, and nurses) in two Nigerian tertiary teaching hospitals (one federal and one state). A total of 220 questionnaires were distributed and 207 were returned (response rate: 94%) and analyzed using SPSS for inferential statistics with a level of significance of P < 0.05. RESULTS: Only 23.7% of the respondents had good knowledge of TXA use in PPH (P < 0.001), and awareness of the recent World Health Organization (WHO) recommendation on the use of TXA for PPH was low (19.8%, P < 0.001). The majority of the respondents had neither prescribed nor dispensed TXA (30%, P < 0.001). Very few respondents used TXA for all cases of PPH (16.4%, P < 0.001). Barriers against its use include nonawareness of the latest WHO recommendation, preference for other uterotonics, and cost of the drug. CONCLUSIONS: There was poor knowledge of TXA, poor awareness of its recommendation, and low use for PPH among different cadres of health care providers.

When to use tranexamic acid for the treatment of major bleeding?

Tranexamic acid (TXA) is an antifibrinolytic agent originally developed for the management of bleeding in the setting of postpartum hemorrhage (PPH). Over the last 15 years, there has been accumulating evidence on the use of TXA for the treatment of active bleeding in a variety of clinical contexts. Clinical trials have shown that the efficacy and safety of TXA for the treatment of bleeding differ according to the clinical context in which it is being administered, timing of administration, and dose. Early administration is important for efficacy, particularly in trauma and PPH. Further studies are needed to understand the mechanisms by which TXA provides benefit, optimal modes of administration and dosing, and its effect in some clinical settings, such as spontaneous intracerebral hemorrhage. There is no evidence that TXA increases the risk of thrombotic events in patients with major bleeding overall. However, there is evidence of increased risk of venous thrombosis in patients with gastrointestinal bleeding. There is also evidence of increased risk of seizures with the use of higher doses. This review summarizes the current evidence for the use of TXA for patients with active bleeding and highlights the importance of generating evidence of efficacy and safety of hemostatic interventions specific to the bleeding contexts-as findings from 1 clinical setting may not be generalizable to other contexts-and that of individual patient assessment for bleeding, thrombotic, and other risks, as well as important logistical and other practical considerations, to optimize care and outcomes in these settings.

Predicting risk of postpartum hemorrhage associated with vaginal delivery of twins: A retrospective study.

Many studies have only focused on the risk factors for postpartum hemorrhage (PPH) in singleton vaginal deliveries and twin cesarean deliveries. We analyzed the factors of influencing PPH occurrence in twin vaginal deliveries and developed a nomogram for clinical application. This retrospective study included 274 pregnant women with twin pregnancies who were hospitalized for delivery from January 2014 to December 2018. The patients opted for vaginal delivery and experienced spontaneous labor. Univariate analysis of PPH risk factors was performed. Multivariate analysis was performed using the least absolute shrinkage and selection operator (LASSO) to obtain relevant factors and build a prediction model, which was presented as a nomogram. The model was internally validated by bootstrap self-sampling method. Model accuracy was evaluated with the concordance index (C-index). There were 36 (13.14%) and 238 (86.9%) patients in the PPH and no PPH groups, respectively. Univariate analysis identified twin chorionicity, hypertensive disorders complicating pregnancy (HDCP), anemia in pregnancy, delivery mode of the second twin, oxytocin use during labor, postpartum curettage, cervical laceration, intrapartum fever, fibrinogen degradation products (FDP), and platelet count (PLT) as significant PPH factors. On multivariate analysis, HDCP, anemia in pregnancy, intrapartum fever, oxytocin use during labor, fetal distress, PLT, direct bilirubin, and FDP were noted as significant PPH factors and were included in the prediction model. A C-index of 0.816 was noted after internal validation, and the calibration curve showed good consistency. We developed a model to predict PPH risk in the vaginal delivery of twin pregnancies and visualized it with a nomogram that can be applied clinically to assess PPH risk and aid PPH prevention.

Efficacy and safety of tranexamic acid in prevention of postpartum hemorrhage: a systematic review and meta-analysis of 18,649 patients.

BACKGROUND: In this meta-analysis, we aimed to update the clinical evidence regarding the efficacy and safety of TXA in the prevention of PPH. METHODS: A literature search of PubMed, Scopus, Web of Science, Google Scholar, and Cochrane Library from inception until December 2022 was conducted. We included randomized controlled trials (RCTs) comparing TXA with a placebo among pregnant women. All relevant outcomes, such as total blood loss, the occurrence of nausea and/or vomiting, and changes in hemoglobin, were combined as odds ratios (OR) or mean differences (MD) in the meta-analysis models using STATA 17 MP. RESULTS: We included 59 RCTs (18,649 patients) in this meta-analysis. For cesarean birth, TXA was favored over the placebo in reducing total blood loss (MD= -2.11 mL, 95%CI [-3.09 to -1.14], P < 0.001), and occurrence of nausea or/and vomiting (OR = 1.36, 95%CI [1.07 to 1.74], P = 0.01). For vaginal birth, the prophylactic use of TXA was associated with lower total blood loss, and higher occurrence of nausea and/or vomiting (MD= -0.89 mL, 95%CI [-1.47 to -0.31], OR = 2.36, 95%CI [1.32 to 4.21], P = 0.02), respectively. However, there were no differences between the groups in changes in hemoglobin during vaginal birth (MD = 0.20 g/dl, 95%CI [-0.07 to 0.48], P = 0.15). The overall risk of bias among the included studies varies from low to high risk of bias using ROB-II tool for RCTs. CONCLUSIONS: This meta-analysis suggested that TXA administration is effective among women undergoing cesarean birth or vaginal birth in lowering total blood loss and limiting the occurrence of PPH. Further clinical trials are recommended to test its efficacy on high-risk populations.

Confusion in the monitoring of coagulation function in pregnant and neonate patients with severe disease: A case reports and brief literature review.

RATIONALE: Different populations have their own unique physiological and pathological characteristics. However, in specialized maternal and child hospitals, there is currently a lack of standardized methods for assessing coagulation dysfunction, both domestically and internationally. PATIENT CONCERNS: A 19-day-old neonate was transferred to neonatal intensive care unit with cyanosis, nasal bleeding for 6 hours, and a consciousness disorder for 5 hours. A 33-year-old woman presented with hydramnios and a 39 + 3week intrauterine pregnancy. All indicators before delivery were normal, but postpartum hemorrhage occurred after delivery. DIAGNOSES: We retrospectively analyzed 1 neonate with pulmonary hemorrhage accompanied by thrombocytopenia and 1 pregnant patient with amniotic fluid embolism. INTERVENTIONS: The new coagulation indicators, such as thrombin-antithrombin complex, plasmin-alpha 2 antiplasmin complex, thrombomodulin, and tissue plasminogen activator-plasminogen activator inhibitor-1 complex, have been indicated to be valuable. In neonates, it is necessary to continuously monitor special items combined with specific therapeutic agents, such as tranexamic acid. In cases where postpartum hemorrhage occurs with low fibrinogen levels, it is essential to effectively identify patients with severe amniotic fluid embolism from a high incidence of specimen clotting. OUTCOMES: The neonate's oxygen saturation stabilized, and after 5 days of treatment with low molecular weight heparin, thrombin-antithrombin complex and plasmin-alpha 2 antiplasmin complex returned to normal levels. The pregnant began to remove the remaining thrombus, the patient's condition recovered, and she had a good prognosis. LESSONS: For pregnant and neonatal critical illnesses, it is necessary to develop personalized coagulation monitoring programs that provide realistic and reasonable treatment recommendations. Such programs should consider the unique physiological and pathological characteristics of different populations to ensure effective management of critically ill patients.

Effect of fibrinogen concentrate on the initial fibrinogen level in trauma and postpartum hemorrhage.

OBJECTIVE: Massive hemorrhage is a serious event that threatens the lives of patients. Fibrinogen concentrate (FC) can control bleeding without causing viral complications and without volume loading, which can happen in transfusion-associated circulatory overload and transfusion-associated acute lung injury. FC application is easy and does not require dissolution or extra devices. It is a cost-effective agent when considering the blood and products used in large quantities. PATIENTS AND METHODS: A total of 67 postpartum hemorrhage (PPH) and trauma patients' medical records, who had ASA I-III classification (The American Society of Anesthesiologists classification of physical status), were obtained. Patients were divided into two groups (fibrinogen level ≤ 100 mg/dl and ≥ 101 mg/dl). The following information was obtained from patient files: demographic parameters, history of operations, and laboratory findings (i.e., complete blood counts, coagulation tests, and fibrinogen levels). Also, the duration of intensive care unit stays and mechanical ventilation application days, the administration of fresh frozen plasma (FFP), erythrocytes, platelets, and FC numbers, and tranexamic acid infusion were recorded. RESULTS: There was no mortality in PPH patients in either group (fibrinogen level ≤ 100 mg/dl and ≥ 101 mg/dl). The mortality rate in trauma patients was significantly higher in the group with fibrinogen levels ≤ 100. A total of 170 g of FC were given to PPH patients and 92 g to trauma patients. There were statistically significant differences between the preoperative PT (prothrombin time), postoperative APTT (activated partial thromboplastin time), postoperative PT, and postoperative INR (international normalized ratio) levels of the patients in the group with fibrinogen levels ≤ 100. Mortality rates were also significantly higher, and hospital stays significantly longer in trauma patients in the group with fibrinogen levels ≤ 100. CONCLUSIONS: Therapy may be considered during massive bleeding and transfusion, as it can help to increase fibrinogen levels quickly and efficiently. Compared with FFP, fibrinogen concentrate may have some advantages in reducing the risk of fluid overload. FFP contains a range of clotting factors, including fibrinogen. It also contains other proteins and fluids that can lead to fluid overload, especially when given in large volumes during massive transfusions.

Tranexamic acid versus misoprostol for management of postpartum hemorrhage: A systematic review and meta-analysis of randomized controlled trials.

AIM: To conduct the first-ever systematic review and meta-analysis of randomized controlled trials (RCTs) on the antihemorrhagic utility and safety of tranexamic acid (TXA) versus misoprostol for management (prevention and/or treatment) of postpartum hemorrhage (PPH). METHODS: Six databases were screened from inception until May 2023 and updated in September 2023. The RCTs were assessed for quality according to the Cochrane's risk of bias tool. The endpoints were summarized as mean difference (MD) or risk ratio (RR) with 95% confidence interval (CI) in a random-effects model. RESULTS: Ten RCTs with 2121 patients (TXA = 1061 and misoprostol = 1060) were analyzed. There was no significant difference between TXA and misoprostol groups regarding the mean intraoperative blood loss (n = 9 RCTs, MD = 17.32 ml, 95% CI [-40.43, 75.07], p = 0.56), mean change in hemoglobin (n = 6 RCTs, MD = 0.11 mg/dl, 95% CI [-0.1, 0.31], p = 0.30), mean hospital stay (n = 2 RCTs, MD = -0.3 day, 95% CI [-0.61, 0.01], p = 0.06), blood transfusion rate (n = 4 RCTs, RR = 0.49, 95% CI [0.16, 1.47], p = 0.2), and rate of additional uterotonic agents (n = 4 RCTs, RR = 1.05, 95% CI [0.72, 1.53], p = 0.81). Leave-one-out sensitivity analysis showed robustness of the results, and there was no evidence of publication bias. Regarding safety endpoints, there was no significant difference between both groups regarding the rates of minor side effects, such as diarrhea, fever, nausea, and vomiting. No patient developed thromboembolic events in the TXA group. CONCLUSION: There was no significant antihemorrhagic efficacy between adjunct TXA and misoprostol for the management of PPH. The safety profile was comparable between both agents.

Tranexamic acid for reduction of blood loss after Caesarean delivery: a cost-effectiveness analysis of the TRAAP2 trial.

BACKGROUND: Prophylactic administration of tranexamic acid is associated with a reduction of blood loss after Caesarean delivery, but cost-effectiveness for this indication has not been assessed. METHODS: We used data from the TRAAP2 trial, a multicentre, double-blinded, RCT aimed at estimating the efficacy of tranexamic acid for preventing postpartum haemorrhage among women undergoing Caesarean delivery. Women recruited at 27 French maternity hospitals from 2018 to 2020 were enrolled before the procedure if they had a Caesarean delivery before or during labour at 34 or more weeks of gestation. The main outcomes were the cost of hospital stay for delivery and the incremental cost per delivery without complication within 90 days after delivery with tranexamic acid compared with placebo. Differences in costs and the incremental net monetary benefit (INMB) were estimated using linear regression models, and the cost-effectiveness probability of tranexamic acid compared with placebo was estimated through the parametric distribution of the INMB. RESULTS: The proportion of women without complications at day 90 was 70.7% in the tranexamic acid group and 66.0% in the placebo group. Mean total costs until occurrence of a complication of interest were €3321 in the tranexamic acid group and €3260 in the placebo group, resulting in a difference between the two groups of 7.2% and €55 after multiple imputation. The adjusted incremental cost-effectiveness ratio was €762 per additional Caesarean delivery without a complication at 90 days after delivery. At a cost-effectiveness threshold of €10,000, the cost-effectiveness probability of tranexamic acid compared with placebo was 99.9%, varying from 5.8% to 100.0% for thresholds from €0 to €10,000 per additional delivery without a complication at day 90. CONCLUSION: Tranexamic acid for the prevention of blood loss is cost-effective in reducing complications after Caesarean delivery at day 90 postpartum. However, the effect size (in cost and effectiveness) is very low. CLINICAL TRIAL REGISTRATION: NCT03431805.

Intravenous tranexamic acid vs. sublingual misoprostol in high-risk women for postpartum haemorrhage following cesarean delivery; a randomised clinical trial.

OBJECTIVE: This study compares the effectiveness of administering sublingual misoprostol combined with oxytocin to that of IV tranexamic acid combined with oxytocin to reduce intra and post-operative blood loss in high-risk women for postpartum haemorrhage (PPH) following cesarean section (CS). METHODS: About 315 high-risk pregnant women undergoing CS participated in this trial. They were randomly assigned into three groups; tranexamic group, misoprostol group, and control group, according to the medication given in the operative theatre. All patients received oxytocin intraoperatively. They were assessed regarding intraoperative blood loss, the incidence of PPH, and the reduction in haemoglobin and hematocrit values. RESULTS: Both tranexamic and misoprostol groups had similar results in reducing intra and post-operative blood loss. However, the reduction in haemoglobin and hematocrit were significantly lower in tranexamic and misoprostol groups compared to the control group (-0.78 ± 0.57 vs. -0.83 ± 0.52 vs. -1.32 ± 0.57 gm/dl, P < 0.001 and - 3.05 ± 1.28 vs. -3.06 ± 1.13 vs. -4.94 ± 1.82%, P < 0.001 respectively). In addition, the estimated blood loss was significantly lower in the tranexamic and misoprostol groups compared to the control group (641.6 ± 271.9 vs. 617.9 ± 207.4 vs. 1002.4 ± 340.7 ml, P < 0.001). CONCLUSION: Both tranexamic acid and misoprostol are equally capable of reducing blood loss, but the results were significantly better compared to using oxytocin alone in high-risk patients. CLINICAL TRIAL REGISTRATION: Registered at www. CLINICALTRIALS: govon07/10/2019 with registration number NCT04117243.

Tranexamic Acid in the Prevention and Treatment of Postpartum Hemorrhage: A Review.

Postpartum hemorrhage (PPH) continues to be one of the leading causes of maternal morbidity and mortality worldwide. The four main causes of PPH are uterine atony, lacerations, retained placenta, and bleeding diathesis. In the patient with PPH, immediate evaluation is needed to diagnose and treat the underlying cause of hemorrhage. Uterotonic agents such as oxytocin remain first line for prevention and treatment of uterine atony. Studies have evaluated the antifibrinolytic tranexamic acid (TXA) as an adjunctive therapy in the prevention and treatment of PPH. TXA has been shown to reduce blood loss, bleeding-associated mortality, and transfusion rates in a variety of clinical settings and thus may serve a role in treating PPH. Current studies have demonstrated that TXA is an effective treatment option with limited risk of adverse events in appropriately selected patients; however, additional studies are needed to further clarify the role of TXA in the prevention of PPH.