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.

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.

Post-Bariatric Abdominoplasty: Analysis of 406 Cases With Focus on Risk Factors and Complications

2020 ◽  
Vol 41 (1) ◽  
pp. 59-71 ◽  
Author(s):  
Torsten Schlosshauer ◽  
Marcus Kiehlmann ◽  
Diana Jung ◽  
Robert Sader ◽  
Ulrich M Rieger
Keyword(s):  
Risk Factors ◽  
Wound Healing ◽  
Surgical Technique ◽  
Significant Risk ◽  
Level Of Evidence ◽  
Increased Risk ◽  
Potential Risk Factors ◽  
Wound Healing Problems ◽  
Bariatric Patients

Abstract Background Post-bariatric patients present a surgical challenge within abdominoplasty because of residual obesity and major comorbidities. In this study, we analyzed complications following abdominoplasty in post-bariatric patients and evaluated potential risk factors associated with these complications. Objectives The authors sought to determine the complications and risk factors following abdominoplasty in post-bariatric patients. Methods A retrospective study of patients who underwent abdominoplasty was performed from January 2009 to December 2018 at our institution. Variables analyzed were sex, age, body mass index (BMI), smoking, surgical technique, operative time, resection weight, drain output, and complications. Results A total of 406 patients were included in this study (320 female and 86 male) with a mean age of 44.4 years and a BMI of 30.6 kg/m2. Abdominoplasty techniques consisted of traditional (64.3%), fleur-de-lis technique (27.3%), and panniculectomy without umbilical displacement (8.4%). Overall complications recorded were 41.9%, the majority of these being wound-healing problems (32%). Minor and major complications were found in 29.1% and 12.8% of patients, respectively. A BMI value of ≥30 kg/m2 was associated with an increased risk for wound-healing problems (P = 0.001). The frequency of total complications was significantly related to age (P = 0.007), BMI (P = 0.004), and resection weight (P = 0.001). Abdominoplasty technique tended to influence total complications. Conclusions This study demonstrates in a fairly large sample of post-bariatric patients (n = 406) that abdominoplasty alone can be performed safely, with an acceptable complication rate. Age, BMI, and resection weight are shown to be significant risk factors for total complications. The role of surgical technique needs to be evaluated further. Level of Evidence: 4

scholarly journals Prevention of venous thromboembolism in hospitalized patients with chronic kidney disease

2013 ◽  
pp. 269-276
Author(s):  
Marcora Mandreoli ◽  
Antonio Santoro
Keyword(s):  
Renal Failure ◽  
Venous Thromboembolism ◽  
Renal Disease ◽  
Case Reports ◽  
Current Evidence ◽  
High Morbidity ◽  
Medical Patients ◽  
Medically Ill ◽  
Increased Risk ◽  
Therapeutic Doses

Despite the high morbidity and mortality associated with venous thromboembolism in hospitalized medical patients with a number of risk factors, and large evidence that prophylaxis is effective, prophylaxis rates remain elusive in medically ill patients. Furthermore, in patients with renal failure, prophylaxis often is omitted or sub-optimal, due to fear of provoking hemorrhage. Patients with end-stage renal disease often have platelet deficits. Low molecular weight heparin (LMWH) therapy may also be difficult to manage in these cases because LMWH clearance is largely dependent on the kidneys. Administration of LMWH to patients with some degree of renal failure may lead to bioaccumulation of anti-Xa activity with an increased risk of bleeding. In recent years, LMWH has largely replaced unfractionated heparin (UFH) for the treatment and prophylaxis of thromboembolic disease. LMWHs have been shown to be superior to UFH in the prevention of venous thromboembolism. They are also easier to administer and do not require laboratory monitoring. However, several case reports and a metaanalysis indicate that the use of LMWHs at therapeutic doses in patients with advanced renal failure can be associated with major bleeding with serious adverse effects. In this paper, we review recent evidence supporting the safety of LMWHs at prophylactic doses in patients with mild or moderate renal disease. Current evidence suggests that bioaccumulation of enoxaparin (the most widely used LMWH) can occur when the drug is used at standard therapeutic doses in patients with severely impaired renal function. This risk can be reduced by empiric dose reduction or monitoring of anti-Xa heparin levels.

scholarly journals Current Evidence for a Role of Neuropeptides in the Regulation of Autophagy

2017 ◽  
Vol 2017 ◽  
pp. 1-10 ◽  
Author(s):  
Elisabetta Catalani ◽  
Clara De Palma ◽  
Cristiana Perrotta ◽  
Davide Cervia
Keyword(s):  
Molecular Mechanisms ◽  
Current Evidence ◽  
Pathological Conditions ◽  
Organ Systems ◽  
Intercellular Signalling ◽  
Physiological Homeostasis ◽  
Response To Stress ◽  
Autophagic Process ◽  
Regulatory Functions

Neuropeptides drive a wide diversity of biological actions and mediate multiple regulatory functions involving all organ systems. They modulate intercellular signalling in the central and peripheral nervous systems as well as the cross talk among nervous and endocrine systems. Indeed, neuropeptides can function as peptide hormones regulating physiological homeostasis (e.g., cognition, blood pressure, feeding behaviour, water balance, glucose metabolism, pain, and response to stress), neuroprotection, and immunomodulation. We aim here to describe the recent advances on the role exerted by neuropeptides in the control of autophagy and its molecular mechanisms since increasing evidence indicates that dysregulation of autophagic process is related to different pathological conditions, including neurodegeneration, metabolic disorders, and cancer.

scholarly journals Role of Bacterial Overgrowth in the Stomach as an Additional Risk Factor for Gastritis

2003 ◽  
Vol 17 (suppl b) ◽  
pp. 13B-17B ◽  
Author(s):  
Gregory Naylor ◽  
Anthony Axon
Keyword(s):  
Gastric Cancer ◽  
Cell Mass ◽  
Bacterial Overgrowth ◽  
Nitroso Compounds ◽  
Current Evidence ◽  
Additional Risk Factor ◽  
Proximal Small Bowel ◽  
Increased Risk ◽  
H Pylori

Gastric bacteria can either be ingested or ascend from the distal bowel; however, their survival is usually limited by gastric acidity and motility. A reduction in gastric acid can result in bacterial overgrowth in the stomach and proximal small bowel, and the number of organisms rises as the intragastric pH rises.The increased risk of noncardia gastric cancer seen in patients with hypochlorhydria may be explained by an excess of nitrites and N-nitroso compounds (NOCs). These compounds are found in the diet of populations with a high gastric cancer risk, but can also be produced by the organisms that exist in the hypochlorhydria stomach. It has long been hypothsized that nitrites and NOCs act as one of the triggers in the atrophy-metaplasia-dysplasia-carcinoma path. However, although indirect data have linked the premalignant changes of metaplasia and dysplasia to NOCs, direct measurement of gastric nitrites and NOCs has not confirmed such a link.The role ofHelicobacter pyloriin bacterial overgrowth is mainly as a cause of hypochlorhydria resulting from atrophic gastritis, leading to a reduction in the parietal cell mass.Acid-suppressing drugs can result in bacterial overgrowth and increased nitrites and NOCs, although there is no current evidence for an increased risk of gastric cancer in patients taking them. One explanation is that the stomach appears to be colonized by different organisms than those in patients with hypochlorhydria for other reasons. There is some evidence that bacterial overgrowth per se can cause gastric inflammation in mice; however, although in humans the degree of gastric inflammation is greater when overgrowth is more prominant this may simply reflect the greater degree of hypochlorhydria in patients with a more severe H pylori-induced inflammation.

scholarly journals Effectiveness and safety of inpatient versus extended venous thromboembolism (VTE) prophylaxis with heparin following major pelvic surgery for malignancy: protocol for a systematic review

2019 ◽  
Vol 8 (1) ◽  
Author(s):  
Bridget Heijkoop ◽  
Natalie Parker ◽  
George Kiroff ◽  
Daniel Spernat
Keyword(s):  
Systematic Review ◽  
Venous Thromboembolism ◽  
Systematic Reviews ◽  
Pelvic Surgery ◽  
Current Evidence ◽  
Cochrane Library ◽  
Vte Prophylaxis ◽  
Optimum Duration ◽  
Number Of Patients ◽  
Increased Risk

Abstract Background Venous thromboembolism (VTE) is a common postoperative complication associated with significant morbidity and mortality. The use of prophylactic heparin postoperatively reduces this risk, and the use of extended duration prophylaxis is becoming increasingly common. Malignancy and pelvic surgery both independently further increase the risk of postoperative VTE and patients undergoing major pelvic surgery for malignancy are at particularly high risk of VTE. However, the optimum duration of prophylaxis specifically in this population currently remains unclear. Methods We will conduct a systematic review of literature in accordance with the Cochrane Handbook for Systematic Reviews of Interventions (Higgins JPT, Green S. Cochrane Handbook for Systematic Reviews of Interventions version 5.1.0.,2011) to evaluate current evidence of the effectiveness and safety of inpatient versus extended VTE prophylaxis with heparin (all forms) following major pelvic surgery for malignancy. We will search PubMed, EMBASE, and the Cochrane Library. Regarding safety, Food and Drug Administration (FDA), and Therapeutic Goods Administration (TGA) websites will be searched, including all levels of evidence. Results will be the postoperative timeframe in which a VTE event can be considered to have been provoked by the surgery, and the number of patients needed to treat with both inpatient and extended prophylaxis to prevent a VTE event in this timeframe, comparing these to determine if there is a significant benefit from extended prophylaxis. Discussion This systematic review will aim to identify the postoperative period in which patients undergoing major pelvic surgery for malignancy are at further increased risk of VTE as a result of their surgery and the optimum duration of heparin VTE prophylaxis with heparin to reduce this risk. Determining this will allow evidence-based recommendations to be made for the optimum duration of heparin VTE prophylaxis post major pelvic surgery for malignancy, leading to improved standards of care that are consistent between different providers and institutions. Systematic review registration In accordance with guidelines, our systematic review was submitted to PROSPERO for consideration of registration on 16/12/17 and was registered on 12/1/18 with the registration number CRD42018068961, and it was last updated on December 1, 2018.

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 Research Progress in the Mechanism of Effect of PRP in Bone Deficiency Healing

2013 ◽  
Vol 2013 ◽  
pp. 1-7 ◽  
Author(s):  
Ning Zhang ◽  
Yong-Ping Wu ◽  
Sheng-Jun Qian ◽  
Chong Teng ◽  
Shuai Chen ◽  
...  
Keyword(s):  
Bone Repair ◽  
Molecular Mechanisms ◽  
Platelet Rich Plasma ◽  
Autologous Blood ◽  
Research Progress ◽  
Current Evidence ◽  
Clinical Settings ◽  
Bone Deficiency ◽  
Defect Repair

Platelet-rich plasma (PRP) therapy is a recently developed technique that uses a concentrated portion of autologous blood to try to improve and accelerate the healing of various tissues. There is a considerable interest in using these PRP products for the treatment used in bone deficiency healing. Because PRP products are safe and easy to prepare and administer, there has been increased attention toward using PRP in numerous clinical settings. The benefits of PRP therapy appear to be promising, and many investigators are exploring the ways in which this therapy can be used in the clinical setting. At present, the molecular mechanisms of bone defect repair studies have focused on three aspects of the inflammatory cytokines, growth factors and angiogenic factors. The role of PRP works mainly through these three aspects of bone repair. The purpose of this paper is to review the current evidence on the mechanism of the effect of PRP in bone deficiency healing.

Homocysteine and thrombosis: from basic science to clinical evidence

2005 ◽  
Vol 94 (11) ◽  
pp. 907-915 ◽  
Author(s):  
Jan Brożek ◽  
Andrzej Szczeklik ◽  
Anetta Undas
Keyword(s):  
Molecular Mechanisms ◽  
Platelet Reactivity ◽  
Current Evidence ◽  
Factor V ◽  
Dna Hypomethylation ◽  
Homocysteine Concentration ◽  
Increased Risk ◽  
Venous Thromboembolic Events ◽  
Venous Thromboembolic ◽  
Artery Disease

SummaryHomocysteine is a sulfhydryl-containing amino acid formed during the metabolism of methionine. Rapidly accumulating evidence links elevated homocysteine levels to thrombosis via several mechanisms such as increased tissue factor expression, attenuated anticoagulant processes, enhanced platelet reactivity, increased thrombin generation, augmented factor V activity, impaired fibrinolytic potential, and vascular injury, including endothelial dysfunction. Molecular mechanisms underlying prothrombotic actions of homocysteine are incompletely understood and involve oxidative stress, DNA hypomethylation, and proinflammatory effects. Current evidence from retrospective and prospective studies supports the concept that higher total plasma homocysteine concentration is associated with increased risk of coronary artery disease, stroke, and venous thromboembolism. Hyperhomocysteinemia is currently considered a relatively weak prothrombotic factor. It is still unclear whether administration of vitamins, that reduce homocysteine levels acting as cofactors of the enzymes involved in the methionine metabolism, may decrease the risk of arterial and/or venous thromboembolic events. Ongoing clinical trials might help clarify this issue.

Predictive Value of D-Dimer Levels for Venous Thromboembolism in Cancer Patients: Results from the Vienna Cancer and Thrombosis Study (CATS)

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 3824-3824
Author(s):  
Cihan Ay ◽  
Rainer Vormittag ◽  
Daniela Dunkler ◽  
Ralph Simanek ◽  
Alexandru-Laurentiu Chiriac ◽  
...  
Keyword(s):  
Venous Thromboembolism ◽  
Cancer Patients ◽  
Predictive Value ◽  
Significant Risk ◽  
Cumulative Probability ◽  
Total Study Population ◽  
Cox Regression Analysis ◽  
Increased Risk ◽  
Diagnosis Of Cancer ◽  
D Dimer

Abstract Venous thromboembolism (VTE) is a frequent complication of cancer, which represents a major cause of morbidity and mortality in cancer patients. Laboratory parameters with a predictive value for VTE could help to assign a patient to a high or low risk group. D-Dimer is a global indicator of coagulation activation and fibrinolysis and is frequently elevated in cancer patients, even without thrombosis. The measurement of D-dimer levels is a widely applied test in the diagnostic work-up of patients with suspected VTE. Prospective observational studies have shown that D-dimer levels have a predictive value for the risk of recurrence in non-cancer patients after the discontinuation of oral anticoagulant treatment. Whether testing for D-Dimer at diagnosis of cancer would be useful for prediction of cancer-associated thrombosis, is not elucidated because up to now appropriately designed prospective studies have not yet been carried out. Therefore, we have assessed D-Dimer levels in cancer patients as risk predictor for VTE and provide a report from the ongoing prospective observational CATS, which was initiated in October 2003. Patients with newly diagnosed cancer or progression of disease that had neither chemotherapy within the last three months, nor radiotherapy nor surgery within the last two weeks were recruited and followed prospectively. Occurrence of VTE and information on the patients’ anti-cancer-treatment within the follow up period were recorded. Observation ended with occurrence of VTE, death or after 2 years. VTE has always been confirmed by imaging. D-Dimer levels were measured with a D-Dimer latex agglutination assay. Kaplan Meier and Cox regression analysis were applied for statistical calculation. Data on 821 patients with cancer (370 women/451 men, median age [IQR]: 62 [53–68] yrs) were available for analyses. Patients were followed for a median observation time of 454 days. Main tumour entities were malignancies of the breast (n=132), lung (n=119), upper (n=35) and lower gastrointestinal tract (n=106), pancreas (n=46), kidney (n=22) and prostate (n=101). Furthermore, 102 patients had high-grade glioma, 94 lymphomas, 17 multiple myeloma and 47 other tumour types. During the observation period VTE occurred in 62 patients (24 female/38 male, median age [IQR]: 60 [50–66] yrs). Elevated levels of D-Dimer (cut-off level 1.44 μg/ml, representing the 75th percentile of the total study population) [hazard ratio (HR): 2.4, 95% CI 1.4–4.0], surgery [HR: 2.3, 95% CI 1.0–5.3] and radiotherapy [HR: 2.3, 95% CI 1.2–4.4] were statistically significant risk factors for VTE in multivariate analysis including D-Dimer, age, sex, surgery, chemotherapy and radiotherapy. The cumulative probability of developing VTE after 6 months was 11.2 % in patients with D-Dimer levels above and 4.2 % in those below the 75th percentile (p=0.003). In conclusion, cancer patients with elevated D-Dimer levels have an approximately 3-fold increased risk for future occurrence of VTE. High levels of D-Dimer independently predict VTE in these patients and D-Dimer measurement at diagnosis of cancer would help identify patients at increased risk for VTE.

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