Pregnancy-associated Venous Thromboembolism Research Articles

Differential serum metabolites in patients with pregnancy-associated venous thromboembolism analyzed using GC-MS/LC-MS untargeted metabolomics

Untargeted metabolomics can be used for the comprehensive analysis of metabolite profiles in biological samples without preset targets, making them particularly suitable for exploring metabolic characteristics and potential mechanisms in complex diseases. Therefore, in this study, we employed gas chromatography–mass spectrometry (GC-MS) and liquid chromatography–mass spectrometry (LC-MS) techniques to analyze the serum metabolic characteristics of patients with pregnancy-associated venous thromboembolism (PA-VTE). In this study, 11 pregnant women with VTE and 11 healthy pregnant women were included in the experimental and control groups, respectively. Using GC-MS, we identified 325 metabolites, with the highest proportion being organic oxygen compounds. Using LC-MS, we identified 3104 metabolites, with the highest proportion being acylcarnitine. The results revealed significant differences in the levels of lipids, organic compounds, and other metabolites between patients compared to healthy pregnant women. Pathways such as pyrimidine metabolism, linoleic acid metabolism, and mineral absorption differed between patients with PA-VTE and controls. Furthermore, we identified biomarkers associated with metabolic processes, such as fatty acids and amino acids (2-hydroxyhexanedioic acid, hexadecenal, palmitoylethanolamide, glycerol-1-phosphate, and N-acetyl-beta-D-glucosamine). These findings revealed the metabolic characteristics of PA-VTE and provided important clues for further research on its pathophysiological mechanisms. Our findings may contribute to the development of new diagnostic markers and support early diagnosis and treatment of PA-VTE.

The prevention, diagnosis and management of pregnancy-associated pulmonary embolism

Pregnancy-associated pulmonary embolism (PE) is a type of venous thromboembolism (VTE) that seriously threatens the lives of pregnant women and has gained more attention in clinical practice. Due to physiological and anatomical characteristics, the incidence of VTE during pregnancy and postpartum is significantly higher than that during non-pregnancy periods. Currently, guidelines widely acknowledge the exploration of appropriate risk assessment models to evaluate the risk of pregnancy-associated VTE and to take corresponding preventive measures from mechanical to medication methods according to different risk levels. For patients suspected of PE, initial assessments can be made based on whether they exhibit clinical manifestations of deep vein thrombosis, with options including vascular compression ultrasonography or chest X-ray examination. Confirmation relies on CT pulmonary angiography or V/Q imaging. For patients with shock, echocardiography can be quickly used for the diagnosis and differential diagnosis of PE. The management of pregnancy-associated pulmonary embolism PE depends on the patient's hemodynamic status, with options including reperfusion therapy or anticoagulation therapy. Extracorporeal membrane oxygenation may also be beneficial in high risk patients. The overall evidence level for the prevention and management of pregnancy-associated PE is low, and further exploration in clinical practice is still needed to promote the safety of pregnant women.

Venous Thromboembolism in Pregnancy: A Review of Diagnosis, Management, and Prevention.

Venous thromboembolism (VTE), which includes deep vein thrombosis (DVT) and pulmonary embolism, is a leading cause of maternal morbidity and mortality worldwide. Physiological changes that occur in a normal pregnancy increase the risk for VTE by 4-5-fold in the antepartum period and 30-60-fold in the immediate postpartum period. Compressive ultrasonography is the diagnostic test of choice for deep vein thrombosis. Both ventilation/perfusion scanning and computed tomography pulmonary angiography can reliably diagnose pulmonary embolism. Anticoagulation for a minimum of 3 months, typically with low molecular weight heparin, is the treatment of choice for pregnancy-associated VTE (PA-VTE). Despite the significant societal burden and potentially devastating consequences, there is a paucity of data surrounding the prevention of PA-VTE, resulting in major variations between international guidelines. This review will summarize the current recommendations for diagnosis, management, and prevention of PA-VTE.

Pregnancy-Associated Venous Thromboembolism.

One of the leading causes of maternal death in the United States is venous thromboembolism (VTE), which is influenced by acquired, genetic, and environmental factors. Pregnancy-associated physiological changes that exhibit the characteristics of Virchow's triad: reduced fibrinolysis, increased coagulation factors, trauma, and venous stasis all raise the risk of VTE. Furthermore, multiple gestations, advanced maternal age, cesarean delivery, and obesity are all pregnancy-associated risk factors that also increase the risk of VTE. Management of VTE during pregnancy can be challenging due to the risks and benefits of anticoagulant therapy and potential hazard for both the fetus and the mother. In this review, we discuss the prevalence, pathogenesis, predisposing factors, and therapeutic options such as systemic thrombolysis, mechanical thrombectomy, and catheter-directed thrombolysis.

VTE Risk Assessment and Prevention in Pregnancy.

Venous thromboembolism (VTE) remains the leading cause of maternal mortality in pregnancy and the postpartum period. In addition to the higher pregnancy-associated baseline VTE risk, there are several well-established risk factors that can further increase the risk of VTE. At present, a thorough interrogation of these risk factors remains our only tool for estimating which pregnant people may be at an increased risk of VTE, and thus potentially benefit from thromboprophylaxis. However, an important knowledge gap still exists surrounding the duration of increased risk and the interaction of risk factors with each other. Furthermore, up to now, once significant risk has been established, prevention strategies have been largely based on expert opinion rather than high-quality data. Recent trials have successfully bridged a proportion of this knowledge gap; however, the challenge of conducting high-quality clinical trials with pregnant people remains. In this article, we provide an update on the recent evidence surrounding VTE risk factors in pregnancy while concurrently outlining knowledge gaps and current approaches to VTE prevention.

Incidence and Risk Factors for Pregnancy-Associated Venous Thromboembolism: Are There Differences between East and West?

Venous thromboembolism (VTE) manifests as thrombus formation in deep vein usually in lower legs which subsequently embolizes to pulmonary artery causing pulmonary embolism and increased risk of morbidity and mortality.[1] Even in this journal there has been much interest in the epidemiology, prognosis, and risk factors for VTE, as well as the pathophysiological mechanisms underlying the propensity to develop this common condition.[2] [3] [4] [5] [6] [7]

Venous thromboembolism in women of childbearing age: insights from the START registry.

Women of childbearing age are exposed to venous thromboembolic risk mainly for pregnancy and use of oral contraceptives. The impact of risk factors (RF) on venous thromboembolism (VTE) in these circumstances is still unclear. In the context of START registry, we aimed to investigate the weight of a series of RF on the occurrence of pregnancy- or combined oral contraceptive (COC)-associated VTE. We selected all women included in the START for VTE occurred between 18-42 years and compared those with a first or recurrent pregnancy/postpartum- (group A) or COC-VTE (group B) with those who had VTE outside these circumstances (group C). Final analysis included a cohort of 532 women. Follow-up data showed that there were no significant differences between the groups in terms of thrombotic and haemorrhagic complications. As for pregnancy-associated VTE, the overall outcome was good in terms of both maternal and fetal prognosis. In a binary model of logistic regression, correcting for potential confounders, VTE family history conferred a significant and independent higher risk of COC-VTE compared with group C. Similarly, comparison between group A and C documented that family history significantly affected the risk of pregnancy-associated VTE. VTE in the group C was significantly associated with older age. Lastly, smoke was a significant risk factor for pregnancy/postpartum VTE when group A and group B were compared. Present data suggest that in the setting of fertile women, family history of VTE has a greater role in predicting COC- and pregnancy/postpartum- VTE than outside these circumstances.

Incidence of Pregnancy-Associated Venous Thromboembolism: Second Nationwide Study.

Pregnancy is a transient risk factor for venous thromboembolism (VTE). This second nationwide study aimed to inspect trend changes in the incidence rate of pregnancy-associated VTE (PA-VTE) during the study period (2014-2018) compared with that reported in a previous study (2006-2010). Using the Korean Health Insurance Review and Assessment Service database, we retrospectively identified all PA-VTE events using both diagnostic and medication codes. Of the 124,228 VTE events, 510 (0.4%) cases of PA-VTE were identified in 499 women (median age: 34 years; range: 20-49 years). The incidence rate of PA-VTE/10,000 deliveries (PA-VTE/104D) in this second study (2.62) was 3.2 times higher than that in the first study (0.82). In the second study, the PA-VTE/104D ratio of women in their 40s (5.46) was three times higher than that of women in their 20s (1.80) (relative risk: 3.03; 95% confidence interval: 2.04-4.51; p < 0.01). The incidence rate for women in their 40s in the second study was 2.3 times higher than that in the first study. PA-VTE/104D cases occurred more frequently in multiparous than in primiparous women, in cesarean section cases compared with vaginal delivery, and in multiple rather than single pregnancies. Most PA-VTE cases occurred during the postpartum period (321/510, 62.9%), of which pulmonary embolism was the most frequently occurring type (231/321, 72%). Advanced maternal age, cesarean section, multiparity, and multifetal pregnancies increased the risk of PA-VTE. Obstetricians need to be cautious of VTE, particularly during the postpartum period, in high-risk pregnant patients.

Incidence of VTE in Pregnant Women with Sickle Cell Gene Mutation(s): A Retrospective Database Analysis

Purpose/Objective(s): The leading cause of pregnancy-associated mortality in Western countries is venous thromboembolism (VTE) with an absolute incidence of 0.025 to 0.1 percent in the general pregnant population. Noubiap et al reported that sickle cell disease (SCD) patients had a significantly higher risk for VTE (pooled OR 4.4, 95%CI 2.6-7.5, p < 0.001), deep vein thrombosis (DVT) (OR 1.1, 95% CI 1.1-1.2, p < 0.001) and pulmonary embolism (PE) (pooled OR 3.7, 95% CI 3.6-3.8, p < 0.001) as compared to patients without SCD [1]. Although sickle cell trait (SCT) and SCD have an increased risk for VTE, the incidence of VTE during pregnancy has not been documented. Our primary objective was to record a composite incidence of VTE among pregnant patients with SCT/SCD. Material/Methods: A retrospective, cross-sectional analysis including pregnant patients with SCT and SCD was conducted at our tertiary care academic medical center. Data was collected between January 2011 and December 2020. Adult women up to 51 years old with hemoglobin electrophoresis proven SCT and SCD were included. Risk factors for VTE such as the patient's body mass index (BMI), COVID status, family history of VTE, and smoking history were included in the analysis. ANOVA and Chi-square tests were used for analysis and to calculate a composite incidence, odds ratio, confidence interval, and p-value. A p-value of <0.05 was considered statistically significant. Data was analyzed using the SAS system. Results: A total of 139 pregnant SCT/SCD patients were included for analysis, out of which, the majority of the patients were SCT (84/139, 60.4%). The mean age at pregnancy was 26.42 (standard deviation 5.72). The type of VTE included DVT 58.3% (14/24) and PE 41.7% (10/24). At our facility, the incidence rate of VTE in pregnancy for SCT/SCD was 17% as compared to 0.025 to 0.1% in the general population. There was no statistically significant difference in the odds of developing VTE between SCD and SCT (OR= 1.09, 95% CI [.45, 2.63]). Only 2.16% of patients had positive COVID infection, as most of the collected data predated the pandemic. Almost one-third of the patients were smokers (45/139) and only 2.88% (4/139) had a family history of VTE. BMI was divided into BMI <30 (38.13%, 53/139) and BMI >30 (61.87%, 86/139). Obesity (OR= 1.03, 95% CI [.4166, 2.56]) and COVID status (OR=2.45, 95% CI [.21, 28.23]) were not found to be significant in our population of patients. Patients with a family history of DVT had a greater odd of developing VTE (OR=50.70, 95% CI [2.63, 977.88]), although the sample may not provide a precise representation of the population mean. Conclusion: Currently, ASH guidelines recommend a conservative approach to VTE prophylaxis unless research suggests benefits [2]. Our analysis found a 17% incidence of pregnancy-associated VTE in our SCT/SCD patients, which is drastically higher than the general population. With such a significant increased incidence in this patient population, especially with current racial disparities in African American maternal mortality rates, more research should be conducted to evaluate the need for thromboprophylaxis/treatment. Additionally, evaluation for specific SCT/SCD guidelines and recommendations to decrease pregnancy-related VTE and mortality rates should be discussed.

Predictors of pregnancy-associated venous thromboembolism: A case-control study.

BackgroundVenous thromboembolism (VTE), manifesting as pulmonary embolism (PE) or deep vein thrombosis (DVT), is the most common cause of morbidity and death during pregnancy and the postpartum period. We conducted this study to describe the predictors of pregnancy-associated VTE (DVT and PE).MethodsA case-control study was conducted at a tertiary care center in Riyadh. A total of 380 patients were included in this study, 180 of whom were diagnosed with pregnancy-associated thrombosis and 200 of them showed no VTE. Demographic data and data on risk factors of VTE were collected by reviewing the medical charts and the risk assessment tool of the Royal College of Obstetricians and Gynecologists, respectively. The main outcome measures were VTE, manifesting as PE or DVT.ResultsThe following factors were identified as the predictors of VTE through multivariate analysis: family history [Odds ratio (OR) = 50.47, 95% Confidence Interval (CI): 6.78–375.64, P < 0.0001)], thrombophilia (OR = 21.99, 95% CI: 2.83–170.63, P = 0.003), and presence of gross varicose veins (OR = 17.15, 95% CI: 3.93–74.87, P < 0.0001).ConclusionsThe findings of this study showed that family history, thrombophilia, and the presence of gross varicose veins were risk factors for VTE, exceeding other transient risk factors. Hence, prophylaxis is highly recommended for those women who present with any of these factors.

Relationship Between ABO Blood Group and Pregnancy Complications

ABO blood group system is the most commonly used blood group classification system in clinic practice. The relevant antigens, A, B and H determinants, are complex carbohydrate molecules that are expressed in red blood cells and other cell lines and tissues. These antigens are determined by the ABO locus located on chromosome 9 (9q34.1-q34.2). ABO blood group is associated with the development of many human diseases, e.g., cardiovascular diseases, infectious diseases, and tumors. The relationship between the ABO blood group of pregnant women and various pregnancy complications, including preeclampsia (PE) and the related diseases, pregnancy associated venous thromboembolism (PA-VTE), gestational diabetes mellitus (GDM), and postpartum hemorrhage (PPH), have become the focus of obstetricians' recent research interest. Herein, we reviewed the relationship between ABO blood group and these pregnancy complications, and found that most of the reported findings supported the following views: 1) Blood type O is a protective factor for PE, while blood type AB increases the risk of PE; 2) blood types other than O are more prone to PA-VTE than blood type O; 3) blood type O or blood type AB may be related to the pathogenesis of GDM; 4) women of blood type O are at higher risks for PPH than those of other blood types. More in-depth epidemiological and genetic studies are needed to confirm these findings in the future. These findings can provide new ideas for researching into the pathogenesis of obstetric diseases and form the theoretical basis for obstetricians to prevent and treat related diseases.

Venous Thromboembolism During Pregnancy and the Postpartum Period: Risk Factors, Diagnostic Testing, and Treatment.

The risk of venous thromboembolism (VTE) increases during pregnancy and the postpartum period. Deep vein thrombosis is the most common VTE during pregnancy, but pulmonary embolism is typically of greater concern as it contributes to far higher morbidity and mortality. Diagnosis and treatment of VTE during pregnancy differ substantially from the general nonpregnant population. This review describes the epidemiology, risk factors, clinical presentation, diagnosis, and treatment of VTE during pregnancy and the postpartum period. First, we reviewed the VTE guidelines from professional societies in obstetrics, cardiology, hematology, emergency medicine, pulmonology, and critical care. Second, we examined references from these documents and used PubMed to identify recent articles that cited the guidelines. Finally, we searched PubMed and Google Scholar for articles published since 2018 that included terms for pregnancy and the epidemiology, risk factors, diagnostic imaging, or treatment of VTE. Venous thromboembolism risk increases throughout pregnancy and peaks shortly after delivery. More than half of pregnancy-related VTE are associated with thrombophilia; other major risks include cesarean delivery, postpartum infection, and the combination of obesity with immobilization. Most VTE can be treated with low molecular weight heparin, but cases of limb- or life-threatening VTE require consideration of thrombolysis and other reperfusion therapies. Venous thromboembolism is far more frequent in antepartum and postpartum women than age-matched controls, and clinical suspicion for VTE in this population should incorporate pregnancy-specific risks. Treatment of limb- or life-threatening antepartum or postpartum VTE requires multispecialty coordination to optimize maternal and fetal outcomes.

Risk factors, diagnosis and management of venous thromboembolic disease in pregnancy.

To gain an understanding of current knowledge on risk factors for pregnancy-associated venous thromboembolism (PA-VTE).To gain an understanding of the diagnosis of PA-VTE.To review up-to-date approaches to preventing and treating PA-VTE.To discuss possible limitations in current research and areas which require improvement.

Preventing Postpartum Venous Thromboembolism in 2022: A Narrative Review.

The postpartum period represents the most critical time for pregnancy-associated venous thromboembolism (VTE), which is responsible for substantial morbidity and an important cause of maternal mortality. The estimated risk of postpartum VTE of about 1/1,000 deliveries can be modulated with the knowledge of maternal and obstetrical risk factors, although a precise estimate remains challenging in individuals. The use of postpartum low-dose low-molecular-weight heparins are tailored at intermediate and high-risk groups to reduce the thrombotic burden, despite the lack of dedicated randomized controlled trials. In this review, we will highlight the contemporary evidence on the risk of postpartum VTE, its stratification and its prevention. We will also discuss our knowledge on the values and preferences of women for postpartum thromboprophylaxis and their adherence to treatment.

Venous Thromboembolism Risk Score and Pregnancy.

Venous thromboembolism (VTE) is a major contributor to maternal morbidity and mortality worldwide. Pregnancy is associated with the development of a baseline hypercoagulable state. The two strongest risk factors for pregnancy-associated VTE are previous VTE and/or high risk thrombophilia. The others risk factors for VTE during pregnancy are well known such as maternal, pregnancy and delivery characteristics. Considering the variation in recommendation in guidelines and low-quality evidence on the prevention, diagnosis and treatment, practice differs between countries and clinical institutions. Some authors developed risk scores, enabling individualized estimation of thrombotic risk during pregnancy, and permitting implementation of a risk-adapted strategy for thromboprophylaxis during pregnancy and postpartum. This review describes the existing VTE risk scores during the antenatal and postnatal period. The important message beyond the score used is that all women should undergo VTE risk factor assessment. The use of a Computerized Clinical Decision Support System for VTE risk assessment should be explored in obstetrics.

Risk stratification for pregnancy-associated venous thromboembolism: Potential role for global coagulation assays.

Risk assessment for venous thromboembolism in pregnancy and the puerperium is currently limited to stratifying clinical surrogate risk factors without high-quality evidence. While the absolute risk of pregnancy-associated venous thromboembolism is low for the vast majority of women, associated morbidity and mortality remains significant. As guidelines for thromboprophylaxis vary widely, some women may be under- or over-anticoagulated, contributing to poor outcomes. New global coagulation assays provide a holistic view of coagulation and may have the potential to detect hypercoagulability in pregnancy, unlike clinically available coagulation assays. However, there are major technical challenges to overcome before global coagulation assays can be realistically proposed as an adjunct to risk assessment for pregnancy-associated venous thromboembolism. This review summarises the literature and controversies in the prediction and prevention of pregnancy-associated venous thromboembolism and outlines the new tools in haematology that may assist in our future understanding of hypercoagulability in pregnancy.

May-Thurner Syndrome in Pregnancy-Associated Venous Thromboembolism.

May-Thurner Syndrome in Pregnancy-Associated Venous Thromboembolism.

Patient- and Health-Care-Provider-Reported Outcomes to Consider in Research on Pregnancy-Associated Venous Thromboembolism

Venous thromboembolism (VTE) in pregnancy can have numerous adverse impacts on patients and health care systems. Ongoing research aimed at improving maternal and fetal/neonatal outcomes is hampered by the lack of patient perspective in determining which outcomes are considered important to assess the effectiveness of interventions. The objective of this study was to elicit outcomes from those who experienced or were at risk for pregnancy-associated VTE (health service users, HSUs) and health care providers (HCPs) involved in their care. Canadian HSUs and HCPs were recruited using convenience and purposive sampling, respectively. Individual, semistructured interviews aimed specifically at eliciting pregnancy-related outcomes were conducted until data saturation was attained. Interviews were audio-recorded and transcribed verbatim. Written transcripts were de-identified and interpretatively analyzed in duplicate to obtain outcomes related to participant experiences. Outcomes were grouped based on a taxonomy developed for medical research and compared between and across interviews with patients and HCPs, and with those obtained through a systematic review of the published literature. We interviewed 10 HSUs and eight HCPs and elicited 52 outcomes, 21 of which have not been reported in the literature. Although the majority of elicited outcomes were in the clinical/physiological core outcome area, both HSUs and HCPs highlighted the importance of outcomes related to functioning/life impact and general wellbeing of mother and baby. These outcomes representing the perspectives of HSUs and HCPs should be considered while conducting trials on pregnancy-associated VTE.

Cancer in pregnancy increases the risk of venous thromboembolism: a nationwide cohort study.

To investigate if cancer in pregnancy causes a higher risk of venous thromboembolism (VTE) during pregnancy and postpartum compared with pregnant women without cancer. A historical prospective cohort study using data from nationwide registries. We assessed all pregnancies in Denmark between 1 January 1977 and 31 December 2017. We linked information concerning cancer diagnosis, pregnancy and VTE diagnosis and potential confounders. Event rates of VTE for women with pre-pregnancy cancer, cancer in pregnancy and without cancer were calculated per 10000 pregnancies and compared using logistic regression analysis. Occurrence of VTE during pregnancy or the postpartum period. A total of 3581214 pregnancies were included in the study and we found 1330 women with cancer in pregnancy. In pregnant women with cancer, the event rate of VTE was 75.2 per 10000 pregnancies compared with 10.7 per 10000 pregnancies in the no cancer group. The findings correspond to an increased adjusted odds ratio of 6.50 (95% CI3.5-12.1) in the cancer in pregnancy group in comparison with the no cancer group. Women with cancer in pregnancy have a markedly higher risk of pregnancy-associated VTE compared with women without cancer. In pregnancy-related VTE risk assessment, the presence of cancer alone may be sufficient to indicate thromboprophylaxis. Cancer in pregnancy increases the risk of VTE during pregnancy and the postpartum period.

Pregnancy-Associated Venous Thromboembolism: Insights from GARFIELD-VTE.

Introduction The risk of venous thromboembolism (VTE) increases during pregnancy and the puerperium such that VTE is a leading cause of maternal mortality. Methods We describe the clinical characteristics, diagnostic strategies, treatment patterns, and outcomes of women with pregnancy-associated VTE (PA-VTE) enrolled in the Global Anticoagulant Registry in the FIELD (GARFIELD)-VTE. Women of childbearing age (<45 years) were stratified into those with PA-VTE ( n = 183), which included pregnant patients and those within the puerperium, and those with nonpregnancy associated VTE (NPA-VTE; n = 1,187). Patients with PA-VTE were not stratified based upon the stage of pregnancy or puerperium. Results Women with PA-VTE were younger (30.5 vs. 34.8 years), less likely to have pulmonary embolism (PE) (19.7 vs. 32.3%) and more likely to have left-sided deep vein thrombosis (DVT) (73.9 vs. 54.8%) compared with those with NPA-VTE. The most common risk factors in PA-VTE patients were hospitalization (10.4%), previous surgery (10.4%), and family history of VTE (9.3%). DVT was typically diagnosed by compression ultrasonography (98.7%) and PE by chest computed tomography (75.0%). PA-VTE patients more often received parenteral (43.2 vs. 15.1%) or vitamin K antagonists (VKA) (9.3 vs. 7.6%) therapy alone. NPA-VTE patients more often received a DOAC alone (30.2 vs. 13.7%). The risk (hazard ratio [95% confidence interval]) of all-cause mortality (0.59 [0.18–1.98]), recurrent VTE (0.82 [0.34–1.94]), and major bleeding (1.13 [0.33–3.90]) were comparable between PA-VTE and NPA-VTE patients. Uterine bleeding was the most common complication in both groups. Conclusion VKAs or DOACs are widely used for treatment of PA-VTE despite limited evidence for their use in this population. Rates of clinical outcomes were comparable between groups.