Elevated venous thromboembolism risk in preeclampsia: molecular mechanisms and clinical impact

2015 ◽  
Vol 43 (4) ◽  
pp. 696-701 ◽  
Author(s):  
Karl Egan ◽  
Barry Kevane ◽  
Fionnuala Ní Áinle
Keyword(s):  
Venous Thromboembolism ◽  
Molecular Mechanisms ◽  
Endothelial Activation ◽  
Extracellular Traps ◽  
Increased Risk ◽  
Consensus Statements ◽  
Maternal Hypertension ◽  
The Subject ◽  
Developed World

Venous thromboembolism (VTE) remains a leading cause of maternal death and morbidity in the developed world. Strategies for prevention of VTE in pregnancy have been the subject of recent guidelines and consensus statements. These guidelines recommend thrombosis prevention in women who have risk factors associated with an elevated VTE risk. Preeclampsia is characterized by maternal hypertension and proteinuria developing after 20 weeks gestation, complicating up to 7% of pregnancies and is associated with a massive annual morbidity and mortality burden. Women with preeclampsia have been shown to be at increased risk of VTE with studies to date suggesting that this risk may be up to 5-fold greater than the risk of pregnancy-associated VTE in the general population. Despite the fact that preeclampsia is so common and potentially devastating, our understanding of its pathogenesis and potential therapeutic strategies remain poor. In addition, the mechanisms underlying the prothrombotic phenotype in preeclampsia are also poorly characterized although a number of potential mechanisms have been postulated. Derangements of platelet and endothelial activation and impairment of endogenous anti-coagulant pathways have been reported and may contribute to the observed VTE risk. Recently, evidence for the role of neutrophil extracellular traps (NETs) and cell-free DNA in the pathogenesis of VTE has emerged and some evidence exists to suggest that this may be of relevance in preeclampsia. Future studies aimed at understanding the diagnostic and potential therapeutic relevance of this procoagulant state are likely to be of enormous clinical benefit for pregnant women affected with this potentially devastating condition.

Pathophysiology of the Venous Thromboembolism Risk in Preeclampsia

2020 ◽  
Vol 40 (05) ◽  
pp. 594-604
Author(s):  
Sarah Kelliher ◽  
Patricia B. Maguire ◽  
Paulina B. Szklanna ◽  
Luisa Weiss ◽  
Karl Ewins ◽  
...  
Keyword(s):  
Venous Thromboembolism ◽  
Blood Coagulation ◽  
Molecular Mechanisms ◽  
Anticoagulant Activity ◽  
Significant Risk ◽  
Screening Tools ◽  
Current Evidence ◽  
Bleeding Tendency ◽  
Increased Risk

AbstractPreeclampsia complicates up to 8% of pregnancies and is a leading cause of fetomaternal morbidity andmortality. Treatment options are limited, with supportive care and delivery of the placenta representing the cornerstone of current management strategies. Derangements in blood coagulation are wellrecognised in this disorder and appear to favour an increased risk of venous thromboembolism among affected women. This risk appears to be most significant in the postpartum period. The mechanisms underlying this increased thrombosis risk remain to be fully elucidated although increased expression of procoagulant factors, endothelial dysfunction, attenuation of endogenous anticoagulant activity and increased platelet activity have been implicated in the prothrombotic tendency. Preeclampsia is also occasionally complicated by life-threatening haemorrhagic events and current evidence suggests that in some severe manifestations of this disease a coagulopathy with a clinical bleeding tendency may be the predominant haemostatic abnormality. Identifying affected women at significant risk of thrombosis and managing the competing thrombotic and haemorrhagic risks continue to be a significant clinical challenge. Derangements in blood coagulation are also implicated in the pathogenesis of preeclampsia; however, the role of antiplatelet or anticoagulant drugs in the prevention and treatment of this disorder remains a source of considerable debate. In addition, the potential role of specific haemostatic markers as diagnostic or screening tools for preeclampsia has also yet to be determined. Further characterisation of the underlying molecular mechanisms would likely be of major translational relevance and could provide insights into the pathogenesis of this disease as well as the associated haemostatic dysfunction.

scholarly journals The Aging Vasculature: Glucose Tolerance, Hypoglycemia and the Role of the Serum Response Factor

2021 ◽  
Vol 8 (5) ◽  
pp. 58
Author(s):  
Hazel Aberdeen ◽  
Kaela Battles ◽  
Ariana Taylor ◽  
Jeranae Garner-Donald ◽  
Ana Davis-Wilson ◽  
...  
Keyword(s):  
Glucose Tolerance ◽  
Molecular Mechanisms ◽  
Serum Response Factor ◽  
Response Factor ◽  
Homeostatic Control ◽  
Older Americans ◽  
The Subject ◽  
Serum Response

The fastest growing demographic in the U.S. at the present time is those aged 65 years and older. Accompanying advancing age are a myriad of physiological changes in which reserve capacity is diminished and homeostatic control attenuates. One facet of homeostatic control lost with advancing age is glucose tolerance. Nowhere is this more accentuated than in the high proportion of older Americans who are diabetic. Coupled with advancing age, diabetes predisposes affected subjects to the onset and progression of cardiovascular disease (CVD). In the treatment of type 2 diabetes, hypoglycemic episodes are a frequent clinical manifestation, which often result in more severe pathological outcomes compared to those observed in cases of insulin resistance, including premature appearance of biomarkers of senescence. Unfortunately, molecular mechanisms of hypoglycemia remain unclear and the subject of much debate. In this review, the molecular basis of the aging vasculature (endothelium) and how glycemic flux drives the appearance of cardiovascular lesions and injury are discussed. Further, we review the potential role of the serum response factor (SRF) in driving glycemic flux-related cellular signaling through its association with various proteins.

Microglia in cerebral ischemia: molecular actions and interactionsThis paper is one of a selection of papers published in this Special Issue, entitled Young Investigator's Forum.

2006 ◽  
Vol 84 (1) ◽  
pp. 49-59 ◽  
Author(s):  
Aaron Y. Lai ◽  
Kathryn G. Todd
Keyword(s):  
Cerebral Ischemia ◽  
Intracellular Signaling ◽  
Molecular Mechanisms ◽  
Extracellular Signals ◽  
Messenger Molecules ◽  
Membrane Bound ◽  
The Subject ◽  
Survey Review ◽  
Selection Of

The precise role of microglia in stroke and cerebral ischemia has been the subject of debate for a number of years. Microglia are capable of synthesizing numerous soluble and membrane-bound biomolecules, some known to be neuroprotective, some neurotoxic, whereas others have less definitive bioactivities. The molecular mechanisms through which microglia activate these molecules have thus become an important area of ischemia research. Here we provide a survey review that summarizes the key actions of microglial factors in cerebral ischemia including complement proteins, chemokines, pro-inflammatory cytokines, neurotrophic factors, hormones, and proteinases, as well several important messenger molecules that play a part in how these factors respond to extracellular signals during ischemic injuries. We also provide some new perspectives on how microglial intracellular signaling may contribute to the seemingly contradictory roles of several microglial effector molecules.

scholarly journals Venous Thromboembolism in COVID-19

2020 ◽  
Vol 120 (12) ◽  
pp. 1642-1653 ◽  
Author(s):  
Sam Schulman ◽  
Yu Hu ◽  
Stavros Konstantinides
Keyword(s):  
Venous Thromboembolism ◽  
Potential Role ◽  
Treatment Guidelines ◽  
Swine Flu ◽  
Thrombolytic Treatment ◽  
Medically Ill ◽  
Risk Assessment Models ◽  
Consensus Statements ◽  
Medically Ill Patients

AbstractThe coronavirus disease 2019 (COVID-19) is our latest pandemic, preceded by the H1N1 swine flu in 2009, which lasted approximately 19 months. One of the special characteristics of COVID-19 is the propensity to cause venous thromboembolism (VTE). Thromboinflammation seems to play a prominent role in the pathogenesis. We will here review some mechanisms in the pathogenesis and discuss some hematological biomarkers, and also whether they serve as useful risk factors for VTE. The role of general risk assessment models for medically ill patients specifically in COVID-19 is appraised. The type of prophylaxis and particularly whether standard or augmented doses of chemoprophylaxis should be used is reviewed based on available evidence. We are also comparing recommendations from 10 different guidance or position/consensus statements. Treatment recommendations for patients with COVID-19 and pulmonary embolism are discussed with current general treatment guidelines as reference. Specifics for patients with COVID-19 are pointed out and the potential role of thrombolytic treatment is explored.

scholarly journals The Role of Stroke as a Trigger for Incident Venous Thromboembolism: Results from a Population-based Case-Crossover Study

TH Open ◽  
2019 ◽  
Vol 03 (01) ◽  
pp. e50-e57
Author(s):  
Vânia Morelli ◽  
Joakim Sejrup ◽  
Birgit Småbrekke ◽  
Ludvig Rinde ◽  
Gro Grimnes ◽  
...  
Keyword(s):  
Venous Thromboembolism ◽  
Acute Stroke ◽  
Crossover Study ◽  
Conditional Logistic Regression ◽  
Population Based ◽  
Red Blood Cell Transfusion ◽  
Odds Ratios ◽  
Case Crossover ◽  
Increased Risk

AbstractStroke is associated with a short-term increased risk of subsequent venous thromboembolism (VTE). It is unclear to what extent this association is mediated by stroke-related complications that are potential triggers for VTE, such as immobilization and infection. We aimed to investigate the role of acute stroke as a trigger for incident VTE while taking other concomitant VTE triggers into account. We conducted a population-based case-crossover study with 707 VTE patients. Triggers were registered during the 90 days before a VTE event (hazard period) and in four preceding 90-day control periods. Conditional logistic regression was used to estimate odds ratios with 95% confidence intervals (CIs) for VTE according to triggers. Stroke was registered in 30 of the 707 (4.2%) hazard periods and in 6 of the 2,828 (0.2%) control periods, resulting in a high risk of VTE, with odds ratios of 20.0 (95% CI: 8.3–48.1). After adjustments for immobilization and infection, odds ratios for VTE conferred by stroke were attenuated to 6.0 (95% CI: 1.6–22.1), and further to 4.0 (95% CI: 1.1–14.2) when other triggers (major surgery, red blood cell transfusion, trauma, and central venous catheter) were added to the regression model. A mediation analysis revealed that 67.8% of the total effect of stroke on VTE risk could be mediated through immobilization and infection. Analyses restricted to ischemic stroke yielded similar results. In conclusion, acute stroke was a trigger for VTE, and the association between stroke and VTE risk appeared to be largely mediated by immobilization and infection.

scholarly journals Women's Mental Health in the Time of Covid-19 Pandemic

2020 ◽  
Vol 1 ◽  
Author(s):  
Florence Thibaut ◽  
Patricia J. M. van Wijngaarden-Cremers
Keyword(s):  
Mental Health ◽  
Violence Against Women ◽  
Health Sector ◽  
Health Issues ◽  
Frontline Workers ◽  
Mental Health Issues ◽  
Increased Risk ◽  
The Subject ◽  
At Home

Even if the fatality rate has been twice higher for men than for women, the Covid-19 pandemic has affected women more than men, both as frontline workers and at home. The aim of our article was to analyze the differences observed in mental health and violence between men and women in the COVID outbreak. For this purpose, we have used all papers available in PubMed between January and July 2020 as well as data from non-governmental associations. We have thus successively analyzed the situation of pregnancy during the pandemic; the specific psychological and psychiatric risks faced by women both as patients and as workers in the health sector, the increased risk of violence against women at home and at workplace and, finally the risk run by children within their families. In conclusion, research on the subject of mental health issues during the Covid-19 pandemic is still scarce, especially in women. We hope that this pandemic will help to recognize the major role of women at home and at the workplace.

scholarly journals SARS-CoV-2 Receptors are Expressed on Human Platelets and the Effect of Aspirin on Clinical Outcomes in COVID-19 Patients

2020 ◽  
Author(s):  
Aditya Sahai ◽  
Rohan Bhandari ◽  
Milka Koupenova ◽  
Jane Freedman ◽  
Mathew Godwin ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Venous Thromboembolism ◽  
Confocal Microscopy ◽  
Cell Surface ◽  
Cerebrovascular Accident ◽  
Human Platelets ◽  
Thrombotic Risk ◽  
Increased Risk ◽  
Inflammatory Drugs

Abstract Coronavirus disease-2019 (COVID-19) caused by SARS-CoV-2 is an ongoing viral pandemic marked by increased risk of thrombotic events. However, the role of platelets in the elevated observed thrombotic risk in COVID-19 and utility of anti-platelet agents in attenuating thrombosis is unknown. We aimed to determine if human platelets express the known SARS-CoV-2 receptor-protease axis on their cell surface and assess whether the anti-platelet effect of aspirin may mitigate risk of myocardial infarction (MI), cerebrovascular accident (CVA), and venous thromboembolism (VTE) in COVID-19. Expression of ACE2 and TMPRSS2 on human platelets were detected by immunoblotting and confirmed by confocal microscopy. We evaluated 22,072 symptomatic patients tested for COVID-19. Propensity-matched analyses were performed to determine if treatment with aspirin or non-steroidal anti-inflammatory drugs (NSAIDs) affected thrombotic outcomes in COVID-19. Neither aspirin nor NSAIDs affected mortality in COVID-19. However, both aspirin and NSAID therapies were associated with increased risk of the combined thrombotic endpoint of (MI), (CVA), and (VTE). Thus, while platelets clearly express ACE2-TMPRSS2 receptor-protease axis for SARS-CoV-2 infection, aspirin does not prevent thrombosis and death in COVID-19. The mechanisms of thrombosis in COVID-19, therefore, appears distinct and the role of platelets as direct mediators of SARS-CoV-2-mediated thrombosis warrants further investigation.

scholarly journals Oxidative Imbalance and Kidney Damage: New Study Perspectives from Animal Models to Hospitalized Patients

Antioxidants ◽  
2019 ◽  
Vol 8 (12) ◽  
pp. 594 ◽  
Author(s):  
Daniela Pellegrino ◽  
Daniele La Russa ◽  
Alessandro Marrone
Keyword(s):  
Risk Factors ◽  
Animal Models ◽  
Molecular Mechanisms ◽  
Public Health Problem ◽  
Kidney Damage ◽  
Major Public Health Problem ◽  
Altered Expression ◽  
Oxidative Balance ◽  
Increased Risk

Chronic kidney disease (CKD) is a major public health problem worldwide and affects both elderly and young subjects. Its main consequences include the loss of renal function, leading to end-stage renal disease, an increased risk of cardiovascular disease, a significant increase in morbidity and mortality, and a decrease in health-related quality of life. This review arose in significant part from work in the authors’ laboratory, complemented by literature data, and was based on a translational approach: we studied the role of many CKD risk factors, such as hypertension, obesity, and oxidative stress/inflammation. The aim was to identify new molecular mechanisms of kidney damage to prevent it through successful behavior modifications. For this purpose, in our studies, both human and animal models were used. In the animal models, we analyzed the mechanisms of renal damage induced by hypertension (spontaneously hypertensive rats) and obesity (cafeteria diet-fed rats), showing that redox disequilibrium in plasma and tissue is extremely important in renal alteration in terms of both oxidative damage (lipid peroxidation, altered expression antioxidant enzymes) and apoptotic pathway (intrinsic/extrinsic) activation. In hemodialysis patients, we explored the correlation between the global oxidative balance and both inflammatory markers and cardiovascular risk, showing a strong correlation between the oxidative index and the blood levels of C-reactive protein and previous cardiovascular events. This multilevel approach allowed us to individually and synergistically analyze some aspects of the complex pathogenic mechanisms of CKD in order to clarify the role of the new amplified risk factors for CKD and to prepare an effective personalized prevention plan by acting on both modifiable and nonmodifiable risk factors.

scholarly journals Respiratory viral infection: a potential “missing link” in the pathogenesis of COPD

2019 ◽  
Vol 28 (151) ◽  
pp. 180063 ◽  
Author(s):  
Dermot Linden ◽  
Hong Guo-Parke ◽  
Peter V. Coyle ◽  
Derek Fairley ◽  
Danny F. McAuley ◽  
...  
Keyword(s):  
Lung Function ◽  
Viral Infection ◽  
Molecular Mechanisms ◽  
Molecular Diagnostic ◽  
Molecular Diagnostic Techniques ◽  
Lung Function Decline ◽  
Respiratory Viral Infection ◽  
Copd Exacerbations ◽  
Increased Risk

Chronic obstructive pulmonary disease (COPD) is currently the third most common cause of global mortality. Acute exacerbations of COPD frequently necessitate hospital admission to enable more intensive therapy, incurring significant healthcare costs. COPD exacerbations are also associated with accelerated lung function decline and increased risk of mortality. Until recently, bacterial pathogens were believed to be responsible for the majority of disease exacerbations. However, with the advent of culture-independent molecular diagnostic techniques it is now estimated that viruses are detected during half of all COPD exacerbations and are associated with poorer clinical outcomes. Human rhinovirus, respiratory syncytial virus and influenza are the most commonly detected viruses during exacerbation. The role of persistent viral infection (adenovirus) has also been postulated as a potential pathogenic mechanism in COPD. Viral pathogens may play an important role in driving COPD progression by acting as triggers for exacerbation and subsequent lung function decline whilst the role of chronic viral infection remains a plausible hypothesis that requires further evaluation. There are currently no effective antiviral strategies for patients with COPD. Herein, we focus on the current understanding of the cellular and molecular mechanisms of respiratory viral infection in COPD.

scholarly journals Effect of aspirin on short-term outcomes in hospitalized patients with COVID-19

2021 ◽  
pp. 1358863X2110127
Author(s):  
Aditya Sahai ◽  
Rohan Bhandari ◽  
Matthew Godwin ◽  
Thomas McIntyre ◽  
Mina K Chung ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Venous Thromboembolism ◽  
Cerebrovascular Accident ◽  
Antiplatelet Agents ◽  
Hospitalized Patients ◽  
Short Term ◽  
Thrombotic Risk ◽  
Increased Risk ◽  
Inflammatory Drugs

Coronavirus disease 2019 (COVID-19) caused by SARS-CoV-2 is an ongoing viral pandemic marked by increased risk of thrombotic events. However, the role of platelets in the elevated observed thrombotic risk in COVID-19 and utility of antiplatelet agents in attenuating thrombosis is unknown. We aimed to determine if the antiplatelet effect of aspirin may mitigate risk of myocardial infarction, cerebrovascular accident, and venous thromboembolism in COVID-19. We evaluated 22,072 symptomatic patients tested for COVID-19. Propensity-matched analyses were performed to determine if treatment with aspirin or nonsteroidal anti-inflammatory drugs (NSAIDs) affected thrombotic outcomes in COVID-19. Neither aspirin nor NSAIDs affected mortality in COVID-19. Thus, aspirin does not appear to prevent thrombosis and death in COVID-19. The mechanisms of thrombosis in COVID-19, therefore, appear distinct and the role of platelets as direct mediators of SARS-CoV-2-mediated thrombosis warrants further investigation.

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