Agnostic identification of plasma biomarkers for postpartum hemorrhage risk.

BACKGROUND: Postpartum hemorrhage (PPH) is difficult to predict, is associated with significant maternal morbidity, and is the leading cause of maternal mortality worldwide. The identification of maternal biomarkers that can predict increased PPH risk would enhance clinical care and may uncover mechanisms that lead to PPH. OBJECTIVE: This retrospective case-control study employed agnostic proteomic profiling of maternal plasma samples to identify differentially abundant proteins in controls and PPH cases. STUDY DESIGN: Maternal plasma samples were procured from a cohort of >60,000 participants in a single institution's perinatal repository. PPH was defined as a decrease in hematocrit of ≥10% or receipt of transfusion within 24 hours of delivery. PPH cases (N=30) were matched by maternal age and delivery mode (vaginal or cesarean) with controls (N=56). Mass spectrometry was used to identify differentially abundant proteins using integrated peptide peak areas. Statistically significant differences between groups were defined by a p-value of <0.05 after controlling for multiple comparisons. RESULTS: By study design, cases and controls did not differ in race, ethnicity, gestational age at delivery, blood type, or pre-delivery platelet count. Cases had slightly, but significantly lower pre- and post-delivery hematocrit and hemoglobin. Mass spectrometry detected 1140 proteins, including 77 proteins for which relative abundance differed significantly between cases and controls (fold change >1.15, P<0.05). Of these differentially abundant plasma proteins, most had likely liver or placental origins. Gene ontology term analysis mapped to protein clusters involved in responses to wound healing, stress response, and host immune defense. Significantly differentially abundant proteins with the highest fold change (prostaglandin D2 synthase, periostin, and several serine protease inhibitors) did not correlate with pre-delivery hematocrit or hemoglobin, but identified PPH cases with logistic regression modeling revealing good-to-excellent area under the operator receiver characteristic curves (AUROC 0.802-0.874). Incorporating pre-delivery hemoglobin with these candidate proteins further improved identification of PPH cases. CONCLUSION: Agnostic analysis of maternal plasma samples identified differentially abundant proteins in controls and PPH cases. Several of these proteins are known to participate in biologically plausible pathways for PPH risk and have potential value for predicting PPH. These findings identify candidate protein biomarkers for future validation and mechanistic studies.

Venous Thromboembolism Risk Factors in Women With Obesity Who Undergo Cesarean Delivery.

Venous thromboembolism (VTE) is a leading cause of maternal mortality. Obesity and cesarean delivery are established risk factors for pregnancy-related VTE. We identified additional risk factors among patients with obesity who underwent a cesarean delivery to identify those who need VTE prophylaxis. We conducted a secondary analysis of data from the Maternal-Fetal Medicine Units Network (MFMU) Cesarean Registry Database using a case-control design. Cases were identified as women with obesity having a pre-pregnancy body mass index of >30 kg/m2, who underwent cesarean delivery and subsequently developed deep venous thrombosis (DVT) or pulmonary embolism (PE). These women were compared to a control group of women with obesity who underwent cesarean delivery but did not develop DVT or PE. Analysis of risk factors associated with VTE was performed using Chi-Square test and Fisher's exact test. We identified 43 VTE cases and 172 controls in the MFMU database. Increased risk of VTE was noted in women with endometritis (OR of 4.58 [95% CI: 1.86-11.2, P = .0004]), receiving a blood transfusion (OR 17.07 [95% CI: 4.46-65.3, P = .0001]), having a coagulopathy (OR 27.73 [95% CI: 3.24-237.25, P = .0003]), and urinary tract infection (OR 2.39 [95% CI: 1.08-5.28, P = .03]). Important risk factors for VTE in women with obesity who undergo cesarean delivery include endometritis, intra- or post-operative transfusion, coagulopathy, and urinary tract infection. The presence of one or more of these factors may help guide provider decision-making regarding whether to administer thromboprophylaxis.

The correlation of non-invasive hemoglobin testing and lab hemoglobin in surgical patients: A systematic review and meta-analysis.

BACKGROUND: The decision regarding intraoperative transfusion has traditionally been based on hemodynamic instability and estimated blood loss. We performed a systematic review to determine the validity of the oximetry method compared to standard of care for hemoglobin measurement. METHODS: A systematic literature review was conducted, and several libraries were searched from inception to March 31,2023. The primary outcome was comparing the mean difference between laboratory-derived hemoglobin and non-invasive, point-of-care hemoglobin measurement. Subgroup analysis included comparing the mean difference in the pediatric population and among female patients. RESULTS: A total of 276 studies were identified, and 37 were included. We found that the pooled mean difference varied qualitatively between adult and pediatric population (p value for heterogeneity <0.001). In adult populations, lab hemoglobin measurements were on average slightly higher than non-invasive measurements (mean difference = 0.23; 95% CI -0.13, 0.59), though there was greater heterogeneity across studies (I2 = 97%, p value = <0.001). In the pediatric population, most studies showed lab hemoglobin to be slightly lower (mean difference = -0.42; 95% CI -0.87 to 0.03). CONCLUSIONS: In general, there was no clinically significant difference in mean hemoglobin among adult and pediatric populations. The percentage of female participants had no effect on the mean difference in hemoglobin.

Development of a Generic Fetal Physiologically Based Pharmacokinetic Model and Prediction of Human Maternal and Fetal Organ Concentrations of Cefuroxime.

BACKGROUND AND OBJECTIVE: Physiologically based pharmacokinetic (PBPK) models for pregnant women have recently been successfully used to predict maternal and umbilical cord pharmacokinetics (PK). Because there is very limited opportunity for conducting clinical and PK investigations for fetal drug exposure, PBPK models may provide further insights. The objectives of this study were to extend a whole-body pregnancy PBPK model by multiple compartments representing fetal organs, and to predict the PK of cefuroxime in the maternal and fetal plasma, the amniotic fluid, and several fetal organs. METHODS: To this end, a previously developed pregnancy PBPK model for cefuroxime was updated using the open-source software Open Systems Pharmacology (PK-Sim®/MoBi®). Multiple compartments were implemented to represent fetal organs including brain, heart, liver, lungs, kidneys, the gastrointestinal tract (GI), muscles, and fat tissue, as well as another compartment lumping organs and tissues not explicitly represented. RESULTS: This novel PBPK model successfully predicted cefuroxime concentrations in maternal blood, umbilical cord, amniotic fluid, and several fetal organs including heart, liver, and lungs. Further model validation with additional clinical PK data is needed to build confidence in the model. CONCLUSIONS: Being developed with an open-source software, the presented generic model can be freely re-used and tailored to address specific questions at hand, e.g., to assist the design of clinical studies in the context of drug research or to predict fetal organ concentrations of chemicals in the context of fetal health risk assessment.

Mechanistic Modeling of the Drug-Drug Interaction Between Efavirenz and Dolutegravir: Is This Interaction Clinically Relevant When Switching From Efavirenz to Dolutegravir During Pregnancy?

Following the 2021 World Health Organization's updated recommendations on the management of HIV infection, millions of people living with HIV are currently switched from efavirenz-based antiretroviral therapy to dolutegravir-based antiretroviral therapy. Pregnant individuals transitioning from efavirenz to dolutegravir might be at increased risk of insufficient viral suppression in the immediate postswitch period because both efavirenz- and pregnancy-related increases in hormone levels induce enzymes involved in dolutegravir metabolism, namely, cytochrome P450 3A4 and uridine 5'-diphospho-glucuronosyltransferase 1A1. This study aimed at developing physiologically based pharmacokinetic models to simulate the switch from efavirenz to dolutegravir in the late second and third trimester. To this end, the drug-drug interaction between efavirenz and the uridine 5'-diphospho-glucuronosyltransferase 1A1 substrates dolutegravir and raltegravir was first simulated in nonpregnant subjects. After successful validation, the physiologically based pharmacokinetic models were translated to pregnancy and dolutegravir pharmacokinetics following efavirenz discontinuation were predicted. Modeling results indicated that, at the end of the second trimester, both efavirenz concentrations and dolutegravir trough concentrations fell below respective pharmacokinetic target thresholds (defined as reported thresholds producing 90%-95% of the maximum effect) during the time interval from 9.75 to 11 days after dolutegravir initiation. At the end of the third trimester, this time interval spanned from 10.3 days to >4 weeks after dolutegravir initiation. These findings suggest that dolutegravir exposure in the immediate post-efavirenz switch period during pregnancy may be suboptimal, leading to HIV viremia and, potentially, resistance. The clinical implications of these findings remain to be substantiated by future studies.

Tranexamic acid for the prevention of postpartum hemorrhage: a cost-effectiveness analysis.

Postpartum hemorrhage is a significant contributor to maternal mortality worldwide and in the United States. Tranexamic acid (TXA) has been shown to reduce PPH complications although it is not routinely recommended for use as prophylaxis to date. To estimate the cost-effectiveness of alternative risk-dictated strategies utilizing prophylactic tranexamic acid for the prevention of postpartum hemorrhage. We constructed a microsimulation-based Markov decision-analytic model estimating the cost-effectiveness of three alternative risk-dictated strategies for tranexamic acid prophylaxis versus the no prophylaxis in a cohort of 3.8 million pregnant women delivering in the United States. Each strategy differentially modified risk-specific hemorrhage probabilities by preliminary estimates of tranexamic acid's prophylactic efficacy. Outcome measures included incremental costs, quality-adjusted life-years, and outcomes averted. Costs and benefits were considered from the healthcare system and societal perspectives over a lifetime time horizon. All intervention strategies were dominant versus no prophylaxis, implying that they were simultaneously more effective and cost-saving. Prophylaxing delivering women irrespective of hemorrhage risk produced the most favorable results overall, with estimated cost savings greater than $690 million and up to 149,505 PPH cases, 2,933 hysterectomies, and 70 maternal deaths averted, per annual cohort. Threshold analysis suggested that tranexamic acid is likely to be cost-saving for health systems at costs below $190 per gram. Our findings suggest that routine prophylaxis with tranexamic acid would likely result in substantial cost-savings and reductions in adverse maternal outcomes in this context. This study is a cost-effectiveness analysis demonstrating cost-savings and reduction in adverse maternal outcomes with routine tranexamic acid as prophylaxis for post-partum hemorrhage.

Acceptability of intramuscular injection of tranexamic acid in postpartum hemorrhage prevention.

BACKGROUND: Newer research comparing routes of medication administration has extended beyond efficacy as a primary endpoint to incorporate patient preference. However, little is known about the preferences of pregnant women in terms of routes of medication administration, specifically with regards to hemorrhage prevention and control. OBJECTIVE: This study aimed to understand the preferences of pregnant women in terms of medical interventions to prevent hemorrhage at the time of delivery. STUDY DESIGN: Surveys were distributed from April 2022 to September 2022 using electronic tablets at a single urban center with an annual delivery volume of 3000 women per year to women >18 years of age who were either currently pregnant or have been pregnant in the past. Subjects were asked to choose their preferred route of administration from the following options: intravenous, intramuscular, or subcutaneous. The primary outcome was patient preference on the route of medication administration during a hemorrhage event. RESULTS: The study cohort included 300 patients, mostly African American (39.8%) followed by White (32.1%), and the majority of the participants ranged from 30 to 34 years of age (31.7%). When asked which method of administration they would prefer to prevent hemorrhage before birth, the results were as follows: 31.1% would prefer intravenous, 23.0% had no preference, 21.2% were unsure, 15.9% preferred subcutaneous, and 8.8% preferred intramuscular administration. In addition, 69.4% of respondents reported that they have never declined or avoided intramuscular administration of medication if recommended by their physician. CONCLUSION: Although some survey participants preferred an intravenous route of administration, 68.9% of subjects were unsure, had no preference, or preferred nonintravenous routes. This information is helpful particularly in low-resource settings where intravenous treatments are not readily available or in urgent clinical situations in which intravenous administration routes are not easily obtainable in high-risk patients.

High risk oral contraceptive hormones do not directly enhance endothelial cell procoagulant activity in vitro.

BACKGROUND: Oral contraceptive (OC) use increases venous thromboembolism risk 2-5-fold. Procoagulant changes can be detected in plasma from OC users even without thrombosis, but cellular mechanisms that provoke thrombosis have not been identified. Endothelial cell (EC) dysfunction is thought to initiate venous thromboembolism. It is unknown whether OC hormones provoke aberrant procoagulant activity in ECs. OBJECTIVE: Characterize the effect of high-risk OC hormones (ethinyl estradiol [EE] and drospirenone) on EC procoagulant activity and the potential interplay with nuclear estrogen receptors ERα and ERß and inflammatory processes. METHODS: Human umbilical vein and dermal microvascular ECs (HUVEC and HDMVEC, respectively) were treated with EE and/or drospirenone. Genes encoding the estrogen receptors ERα and ERß (ESR1 and ESR2, respectively) were overexpressed in HUVEC and HDMVEC via lentiviral vectors. EC gene expression was assessed by RT-qPCR. The ability of ECs to support thrombin generation and fibrin formation was measured by calibrated automated thrombography and spectrophotometry, respectively. RESULTS: Neither EE nor drospirenone, alone or together, changed expression of genes encoding anti- or procoagulant proteins (TFPI, THBD, F3), integrins (ITGAV, ITGB3), or fibrinolytic mediators (SERPINE1, PLAT). EE and/or drospirenone did not increase EC-supported thrombin generation or fibrin formation, either. Our analyses indicated a subset of individuals express ESR1 and ESR2 transcripts in human aortic ECs. However, overexpression of ESR1 and/or ESR2 in HUVEC and HDMVEC did not facilitate the ability of OC-treated ECs to support procoagulant activity, even in the presence of a pro-inflammatory stimulus. CONCLUSIONS: The OC hormones EE and drospirenone do not directly enhance thrombin generation potential of primary ECs in vitro.

Building the foundation for a community-generated national research blueprint for inherited bleeding disorders: research to advance the health of people with inherited bleeding disorders with the potential to menstruate.

BACKGROUND: People who have or had the potential to menstruate (PPM) with inherited bleeding disorders (BD) face particular challenges receiving appropriate diagnosis and care and participating in research. As part of an initiative to create a National Research Blueprint for future decades of research, the National Hemophilia Foundation (NHF) and American Thrombosis and Hemostasis Network conducted extensive all-stakeholder consultations to identify the priorities of PPM with inherited BDs and those who care for them. RESEARCH DESIGN AND METHODS: Working group (WG) 4 of the NHF State of the Science Research Summit distilled community-identified priorities for PPM with inherited BDs into concrete research questions and scored their feasibility, impact, and risk. RESULTS: WG4 identified important gaps in the foundational knowledge upon which to base optimal diagnosis and care for PPM with inherited BDs. They defined 44 top-priority research questions concerning lifespan sex biology, pregnancy and the post-partum context, uterine physiology and bleeding, bone and joint health, health care delivery, and patient-reported outcomes and quality-of-life. CONCLUSIONS: The needs of PPM will best be advanced with research designed across the spectrum of sex and gender biology, with methodologies and outcome measures tailored to this population, involving them throughout.

Up to 1% of cisgender women and girls have an inherited bleeding disorder (BD). Common symptoms include heavy menstrual bleeding (HMB), heavy bleeding after giving birth known as post-partum hemorrhage (PPH), nose bleeds, bleeding from the mouth, and excessive bleeding after surgery or procedures. They can also experience bleeding into their muscles, joints, and even into the brain. Uterine bleeding, such as from HMB and PPH, can impact the lives of anyone who has or had a uterus, a group we designate as people who have or had the potential to menstruate (PPM).Many PPM with an inherited BD do not receive diagnosis, treatment, and care needed due to a lack of expertise among health care professionals and the public, misunderstanding, and bias. Uncertainty about "normal" versus "abnormal" bleeding can contribute to a lack of diagnosis, treatment, and care. Language, such as the label of "carrier," can be a barrier to accessing treatment and care for PPM.People with inherited BDs, health care professionals with various expertise and focus, and researchers worked together to identify the research that would most improve the lives of PPM, in six focus areas where there are major gaps in knowledge and the lack of standards required for accurate diagnosis.

An update to tranexamic acid trends during the peripartum period in the United States, 2019 to 2021.

BACKGROUND: Results from the 2017 World Maternal Antifibrinolytic trial found that patients who received tranexamic acid during delivery had significantly lower rates of death and hysterectomy. Several months after the World Maternal Antifibrinolytic trial publication, American College of Obstetricians and Gynecologists endorsed the consideration of tranexamic acid usage when traditional uterotonics fail during postpartum hemorrhage. Since then, tranexamic acid usage has become more mainstream for the treatment of postpartum hemorrhage. OBJECTIVE: This study aimed to evaluate tranexamic acid trends in obstetrics both temporally and geographically within the United States. Additional outcomes included patient demographics and perinatal outcomes. STUDY DESIGN: This retrospective cohort study included 19 hospitals divided into East, Central, and West geographic regions within the Universal Health Services, Incorporated network. Rates of tranexamic acid use were compared from July 2019 through June 2021. Patient demographics and perinatal outcomes were analyzed for tranexamic acid recipients. RESULTS: During the two-year study period, 3.2% (1580/50,150) of patients received tranexamic acid during delivery. The western region of the United States demonstrated increased tranexamic acid use over the 2-year study period. Recipients of tranexamic acid were more likely to have a history of postpartum hemorrhage (P<.0001), chronic hypertension (P<.0001), preeclampsia (P<.0001), and/or diabetes (P=.004). Patients who received tranexamic acid did not have an increased likelihood of venous thromboembolism in comparison with those who did not receive tranexamic acid (8 [0.5%] vs 226 [0.5%]; P=.77). Of those who received tranexamic acid, 53.2% (840/1580) had an estimated blood loss <1000 mL. CONCLUSION: Nationally, a higher percentage of patients received tranexamic acid without a postpartum hemorrhage diagnosis compared with previous studies, and the western region of the United States had an overall increased use of tranexamic acid during delivery compared with previous years. There was no increased risk of venous thromboembolism in those who received tranexamic acid, regardless of postpartum hemorrhage diagnosis.

Recent trends in tranexamic acid use during postpartum hemorrhage in the United States.

INTRODUCTION: Postpartum hemorrhage (PPH) was the second leading cause of maternal death, accounting for approximately 14% of all pregnancy-related deaths between 2017 and 2019 in the United States. Several large multi-center studies have demonstrated decreased PPH rates with the use of tranexamic acid (TXA). Little data exists regarding the prevalence of TXA use in obstetric patients. METHODS: We identified over 1.2 million US pregnancies between January 1, 2015 and June 30, 2021, with and without PPH by International Statistical Classification of Disease and Related Health Problems, Tenth Revision codes using Cerner Real-World Database™. TXA use and patient characteristics were abstracted from the electronic medical record. RESULTS: During delivery, TXA was used approximately 1% of the time (12,394 / 1,262,574). Pregnant patients who did and did not receive TXA during delivery had similar demographic characteristics. Pregnant patients who underwent cesarean delivery (4,356 / 12,394), had a term delivery (10,199 / 12,394), and had comorbid conditions were more likely to receive TXA during hospitalization for delivery. The majority of TXA was use was concentrated in Arizona, Colorado, Idaho, New Mexico, Nevada, Utah, and Wyoming. During the study period the use of TXA increased in both patients with PPH and those without. CONCLUSION: The data illustrate a rapid increase in the use of TXA after 2017 while the total number of pregnancies remained relatively constant. The observed increase in TXA use may reflect changing practicing patterns as the support for use of TXA in the setting of PPH prophylaxis increases.

Impact of anemia and thrombocytopenia on postpartum hemorrhage risk among women with term singleton pregnancy.

Both thrombocytopenia (platelet count < 150 × 103/µL) and anemia have been associated with postpartum hemorrhage (PPH). However, the impact of thrombocytopenia on PPH risk among women with mild and severe anemia is unknown. We sought to evaluate the association between thrombocytopenia and anemia in increasing risk of PPH. We performed a secondary analysis of a retrospective cohort of pregnant women from 19 hospitals across the United States from 2016 to 2021. Women who had a term singleton pregnancy and hematocrit (Hct) ≤ 33% at delivery were included in the study. The primary outcome was PPH (defined as blood loss ≥ 1000 mL or blood transfusion). We also analyzed the effect of severe anemia (Hct < 28%) on the association between PPH and thrombocytopenia. Chi-squared tests and Fisher's exact tests were used for categorical variables and an independent t-test was used for continuous variables. There were 20,808 women who met our inclusion criteria, of which 1793 (8.6%) had platelet count < 150 × 103/µL. The prevalence of PPH was 6.4%. Compared with women with normal platelet count, those with thrombocytopenia had 1.3-fold higher odds of PPH [6.8% vs. 4.5%, adjusted OR 1.3 (1.1-1.7)]. Platelet count ≥ 150 × 103/µL was associated with decreased odds of PPH among patients with hct between 28 and 33% and hct < 28%. In conclusion, anemic women with term singleton pregnancies who delivered with thrombocytopenia had a higher frequency of PPH. Normal platelet count at delivery was protective against PPH in the setting of anemia regardless of severity.

Emerging technology for early detection and management of postpartum hemorrhage to prevent morbidity.

Despite advances in hemorrhage detection and management, postpartum hemorrhage remains the single leading cause of maternal death worldwide. Within the United States, hemorrhage is the leading cause of maternal death on the day of delivery and within the first week after delivery. Blood transfusion after hemorrhage represents a large proportion of severe maternal morbidity during and after delivery. Blood loss during delivery has historically been assessed visually by inspecting soiled pads, linens, and laparotomy sponges. These methods underestimate the volume of blood loss by as much as 40%, becoming increasingly inaccurate as blood loss increases. Young, healthy obstetrical patients compensate for blood loss via peripheral vasoconstriction, maintaining heart rate and blood pressure in a normal range until over 1 L of blood has been lost. A significant decrease in blood pressure along with marked tachycardia (>120 bpm) may not be seen until 30% to 40% of blood volume has been lost, or 2.0 to 2.6 L in a healthy term pregnant patient, after which the patient may rapidly decompensate. In resource-poor settings especially, the narrow window between the emergence of significant vital sign abnormalities and clinical decompensation may prove catastrophic. Once hemorrhage is detected, decisions regarding blood product transfusion are routinely made on the basis of inaccurate estimates of blood loss, placing patients at risk of underresuscitation (increasing the risk of hemorrhagic shock and end-organ damage) or overresuscitation (increasing the risk of transfusion reaction, fluid overload, and alloimmunization). We will review novel technologies that have emerged to assist both in the early and accurate detection of postpartum hemorrhage and in decisions regarding blood product transfusion.

Recognizing who is at risk for postpartum hemorrhage: targeting anemic women and scoring systems for clinical use.

Iron deficiency anemia during pregnancy is a common concern, affecting 38% of women worldwide and up to 50% in developing countries. It is defined differently throughout all 3 trimesters. It has several detrimental effects on pregnancy outcomes for both the mother and the fetus, such as increasing the risk for postpartum depression, preterm delivery, cesarean delivery, preeclampsia, and low birthweight. Management of iron deficiency anemia is done classically via oral iron supplementation. However, recent evidence has shown that intravenous iron is a good alternative to oral iron if patients are unable to tolerate it, not responding, or present with a new diagnosis very late in pregnancy. Management of iron deficiency anemia was demonstrated to be protective against postpartum hemorrhage. Other ways to prevent postpartum hemorrhage include improving prediction tools that can identify those at risk. Several risk assessment kits have been developed to estimate the risk for postpartum hemorrhage among patients and have been proven useful in the prediction of patients at high risk for postpartum hemorrhage despite limitations among low-risk groups. More comprehensive tools are also being explored by determining clinically relevant factors through nomograms, with some proving their efficacy after implementation. Machine learning is also being used to develop more complete tools by including risk factors previously not accounted for. These newer tools, however, still require external validation before being adopted despite promising results under testing conditions.

Pharmacoethics and pregnancy: Overcoming the therapeutic orphan stigma.

There is paucity of evidence to support clinical decision making and counselling related to medication use in pregnancy. Despite multiple efforts from legislative bodies and advocacy groups, the inclusion of pregnant women in clinical drug trials assessing efficacy and safety remains scarce. Pregnancy can be complicated by multiple comorbidities that require pharmacological intervention; these interventions primarily target the pregnant woman but also sometimes have secondary effects for the foetus. The US Food and Drug Administration has issued multiple guidance documents on incorporating pregnant women in clinical trials to aid pharmaceutical companies in designing a protocol to ensure safety and adherence to ethical standards. Advances in paediatric pharmacology studies provide lessons for researchers on the best practice of designing clinical trials with inclusion of patients from special populations. In this review, we present the status of pregnant women in clinical trials, highlighting the ethical stigma and possible future directives.

Knowledge, Attitude, and Beliefs of Medication Use in Pregnancy in an Urban Tertiary Care Center.

Medication use in pregnancy is common. However, there is a gap in the literature assessing the knowledge of pregnant individuals about medication use in pregnancy. The aim of our study is to assess the knowledge, attitudes, and beliefs of pregnant people on medication use in pregnancy. We conducted a cross-sectional survey questionnaire that was completed by pregnant patients from December 2021 to January 2022. The survey included questions regarding knowledge, attitude, and sources for obtaining information about medication use in pregnancy and general statements from the Beliefs about Medicines Questionnaire (BMQ). A total of 150 participants completed the survey. Most patients reported that a person should know that medication use for chronic diseases must be modified during pregnancy and that medications can be used in any trimester of pregnancy. Most reported that medication use can lead to fetal growth restriction and maternal bleeding. The mean scores (SDs) on the BMQ-General for the overuse, harm, and benefit statements were 8.7 (2.4), 8.2 (3.1), and 15.7 (2.8). Even though medication use in pregnancy is common, it is an area of concern to pregnant patients. More research on identifying the risks of different medicines used in pregnancy is thus needed.

Alternative routes to intravenous tranexamic acid for postpartum hemorrhage: A systematic search and narrative review.

OBJECTIVE: To review available data on tranexamic acid (TXA) plasma concentration needed to inhibit fibrinolysis and the time to achieve this concentration when giving TXA by different routes in humans. To identify ongoing trials assessing alternatives to intravenous TXA administration. METHODS: We updated two previous systematic reviews by searching MEDLINE, EMBASE, OviSP, and ISI Web of Science from database inception to July 2021. We also searched the WHO International Clinical Trials Registry Platform for ongoing trials to July 2021. Titles and abstracts were screened for relevant trials. Two reviewers independently reviewed and agreed the trials to be included. RESULTS: Plasma TXA concentrations over 10 mg/L provide near maximal inhibition of fibrinolysis, with concentrations over 5 mg/L providing partial inhibition. Oral TXA tablets take about 1 h to reach a plasma concentration of 5 mg/L in postpartum women. Studies in healthy volunteers and shocked trauma patients show that intramuscular TXA achieves a plasma level of over 10 mg/L within 15 min. One trial is ongoing to determine the pharmacokinetics of intramuscular and oral solution TXA in pregnant women. CONCLUSION: Intramuscular TXA in healthy volunteers and shocked trauma patients reaches therapeutic concentration rapidly. Oral TXA tablets take too long to reach the minimum therapeutic concentration in postpartum women.

Effect of implementation of a colorimetric quantitative blood loss system for postpartum hemorrhage.

OBJECTIVE: To evaluate if the implementation of a colorimetric quantitative blood loss (QBL) system during cesarean delivery improves clinical outcomes. METHODS: We conducted a retrospective cohort analysis after cesarean section before and after implementation of the Triton based colorimetric QBL system. Prevalence of postpartum hemorrhage, amount of blood products transfused, length of hospitalization, and rates of intensive care unit (ICU) admission were compared. RESULTS: A total of 2221 patients were included. There were 1192 patients in the pre-intervention group and 1029 patients in the post-intervention group. There was no significant difference between groups in the prevalence of postpartum hemorrhage (8.6% vs 9.3%, P = 0.57), amount of packed red blood cells (pRBCs) transfused (45 vs 30, P = 0.41) or average length of hospital stay in days (3.0 vs 3.0, P = 0.37). There was a statistically significant decrease in ICU admissions between the pre- and post-intervention groups (2.2% vs 1.0%, P = 0.02). CONCLUSION: There was no effect of implementation of the colorimetric QBL application system on diagnosis of postpartum hemorrhage, amount of blood products transfused, or length of hospital stay. Although a significant decrease in ICU admissions was observed, we could not determine if these transfers were hemorrhage related.

Disparities in obstetric hemorrhage outcomes.

Both the maternal and fetal outcomes of pregnancy vary greatly according to a pregnant woman's community and her condition. The most devastating outcome is the death of a mother. In 2017, there were ≈295,000 maternal deaths globally with dramatic differences in maternal mortality based on geographic region, country, and women's underlying conditions. Worldwide, the leading cause of maternal death is hemorrhage, comprising 94% of maternal deaths, with most cases occurring in low- or middle-income countries. Whether a hemorrhage originates from inside the uterus (80%-90%), from lacerations or incisions (10%-20%), or from an underlying coagulopathy (<1%), an acute acquired coagulopathy will evolve unless the hemorrhage is controlled. In low- or middle-income countries, the full range of resources to control hemorrhage is not available, but besides the usual obstetric measures, blood availability, hemostatic medication, and hematologic expertise are necessary to save mothers' lives. Hemostasis and thrombosis experts can address the disparities in obstetric hemorrhage outcomes not only as providers but as consultants, researchers, and advocates.