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Association of Thrombophilia and Inflammation with Post-Thrombotic Syndrome

血栓形成倾向和炎症与血栓后综合征的关联

基本信息

批准号：
7393101
负责人：
MARY CUSHMAN
金额：
$ 33.37万
依托单位：
UNIVERSITY OF VERMONT & ST AGRIC COLLEGE
依托单位国家：
美国
项目类别：
财政年份：
2006
资助国家：
美国
起止时间：
2006-05-12 至 2011-03-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7393101
关键词：
Address Adipocytes Adult Affect Age Anatomy Anticoagulant therapy Anticoagulants Anticoagulation Arteries Basic Science Bilateral Biological Biological Markers Blood Case-Control Studies Chronic Chronic Disease Clinical Clinical Trials Collaborations Complication DNA Deep Vein Thrombosis Depth Development Diagnosis Disease Edema Embolism Enzyme-Linked Immunosorbent Assay Epidemiology Ethnic Origin Evaluation Follow-Up Studies Functional disorder Funding General Population Genetic Genetic Predisposition to Disease Genotype Hereditary Disease Hospitalization Incidence Inflammation Inflammatory Inherited Intervention Investigation Laboratories Lead Leg Lower Extremity Lung Measures Medical Medical History Minor Molecular Molecular Epidemiology Molecular Genetics Natural History Numbers Obesity Obstruction Operative Surgical Procedures Orthopedic Surgery procedures Other Finding Participant Patient Care Patients Peripheral Persons Physical Examination Population Population Study Postoperative Period Postphlebitic Syndrome Protein C Deficiency Proteins Proteomics Range Rate Recording of previous events Recurrence Reflux Relative Risks Reporting Research Research Personnel Review, Systematic (PT)Risk Risk Marker Role Sampling Severities Skin Source Specimen Staging Stroke Structure of superficial vein Symptoms Syndrome Techniques Testing Thinking Thrombophilia Thrombosis Time Translating Translations Trauma Ulcer Ultrasonography United States Varicose Ulcer Veins Venous Venous Thrombosis Woman Work assay development base case control chronic pain cohort cost deep vein disability disease classification experience genetic epidemiology genetic variant innovation interest kindred men monocyte multidisciplinary novel peripheral blood prevent prospective

项目摘要

Deep vein thrombosis (DVT) or pulmonary embolus affect 1-3 per 1000 yearly of the adult population, or nearly 200,000 per year, with an incidence that rises exponentially with age. The burden of venous thrombosis predominantly involves DVT, which is complicated by post-thrombotic syndrome (PTS) in 20- 50% of cases. PTS has a spectrum from mild edema to disabling symptomatic disease with trophic skin changes, chronic pain, and venous skin ulceration. While PTS is thought to occur as a result of damage to the venous valves with resultant reflux or chronic venous obstruction limiting outflow, additional etiologic determinants of PTS have not been extensively studied. We propose a population-based study to evaluate the molecular determinants of chronic peripheral venous disease (CPVD) in a multi-ethnic general population sample, the San Diego Population Study (SDPS). Participants had detailed physical examination and duplex leg ultrasound to establish presence of CPVD based on anatomic and clinical findings. We will address the following hypotheses: 1.Among those with hereditary disorders associated with the hypercoagulable state ("hereditary thrombophilia") there will be an increased risk of deep functional venous disease (DFD) assessed by duplex ultrasound and of superficial venous functional disease (SFD) when it occurs in the absence of DFD and together with clinical features of PTS. 2. There will be an increased risk of DFD or SFD with features of PTS, among participants with higher levels of biomarkers reflecting different aspects inflammation. 3. Given the association of obesity with the risk of CPVD and PTS, there will be an increased risk of DFD or SFD with features of PTS in association with higher levels of biomarkers reflecting adipocyte products. To test these hypotheses phenotypic and genetic molecular biomarkers will be measured in stored biological specimens of the SDPS participants including 370 control participants and 370 cases of CPVD, focusing on post-thrombotic syndrome. Findings will allow hypotheses to be formed concerning etiologic factors in the development of PTS after clinically diagnosed or clinically silent DVT. PTS and CPVD affect -2.5 million people in the United States; 20% develop severe disease with venous ulcers. Resultant disability is estimated at 2 million lost workdays/year and medical costs as $300 million yearly. Findings here can form the basis for development of new therapies to treat, and moreover prevent,PTS.

深静脉血栓形成(DVT)或肺血栓每年影响成年人口的1-3人，或每年近20万人，发病率随着年龄的增长呈指数增长。静脉的负担血栓形成主要累及深静脉血栓，并发血栓后综合征(PTS)的20- 50%的病例。PTS的范围从轻度浮肿到皮肤营养不良的症状性疾病慢性疼痛和静脉性皮肤溃疡。而PTS的发生被认为是由于静脉瓣膜合并反流或慢性静脉阻塞限制流出，其他病因 PTS的决定因素尚未得到广泛研究。我们提出了一项基于人口的研究来评估多民族人群慢性周围静脉疾病的分子决定因素样本，圣地亚哥人口研究(SDPS)。参与者进行了详细的体检和复印腿部超声根据解剖和临床结果确定是否存在CPVD。我们将解决以下假设：1.在与高凝状态相关的遗传性疾病中 (“遗传性血栓形成症”)患深静脉功能性疾病(DFD)的风险会增加。通过双功能超声和浅表静脉功能疾病(SFD)的评估无DFD，并伴有PTS的临床特征。2.DFD或SFD的风险将会增加具有PTS特征的参与者中，具有反映不同方面的较高水平的生物标志物发炎。3.考虑到肥胖与CPVD和PTS的风险之间的关联，伴有PTS特征的DFD或SFD的风险与较高水平的反映脂肪细胞的生物标志物相关产品。为了验证这些假设，表型和遗传分子生物标记物将在存储的 SDPS参与者的生物标本包括370名对照参与者和370例CPVD患者，重点关注血栓形成后综合征。这些发现将允许形成关于病因学的假说临床确诊或临床无症状的深静脉血栓形成后PTS发生的因素。PTS和CPVD的影响 -美国有250万人；20%的人患有严重的静脉溃疡。由此导致的残疾估计每年损失200万个工作日，医疗费用为3亿美元。这里的发现可以形成为开发治疗和预防PTS的新疗法奠定了基础。