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

• 批准号: 7233208
• 负责人: MARY CUSHMAN
• 金额: $ 37.03万
• 依托单位: UNIVERSITY OF VERMONT & ST AGRIC COLLEGE
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-05-12 至 2009-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7233208
• 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

Description (provided by Applicant): 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.

描述（由申请人提供）： 深静脉血栓 (DVT) 或肺栓塞每年影响每 1000 名成年人中 1-3 人，即每年近 200,000 人，其发病率随着年龄的增长呈指数级上升。静脉血栓形成的负担主要涉及 DVT，20-50% 的病例会并发血栓后综合征 (PTS)。 PTS 的症状范围从轻度水肿到导致皮肤营养改变、慢性疼痛和静脉性皮肤溃疡的致残性症状性疾病。虽然 PTS 被认为是由于静脉瓣膜损伤导致反流或限制流出的慢性静脉阻塞而发生的，但 PTS 的其他病因决定因素尚未得到广泛研究。我们提出了一项基于人群的研究，以评估多种族一般人群样本中慢性外周静脉疾病 (CPVD) 的分子决定因素，即圣地亚哥人口研究 (SDPS)。参与者进行了详细的身体检查和双功能腿部超声检查，以根据解剖学和临床发现确定 CPVD 的存在。我们将提出以下假设： 1. 在患有与高凝状态相关的遗传性疾病（“遗传性血栓形成倾向”）的患者中，通过双功能超声评估患深部功能性静脉疾病（DFD）和浅表静脉功能性疾病（“遗传性血栓形成倾向”）的风险会增加。 SFD）当它在没有 DFD 的情况下发生并且与 PTS 的临床特征一起发生时。 2. 在反映炎症不同方面的生物标志物水平较高的参与者中，患有具有 PTS 特征的 DFD 或 SFD 的风险会增加。 3. 鉴于肥胖与 CPVD 和 PTS 风险之间的关联，具有 PTS 特征的 DFD 或 SFD 风险将会增加，并与反映脂肪细胞产物的较高水平的生物标志物相关。为了检验这些假设，将对 SDPS 参与者储存的生物样本中的表型和遗传分子生物标志物进行测量，其中包括 370 名对照参与者和 370 名 CPVD 病例，重点关注血栓后综合征。研究结果将有助于形成关于临床诊断或临床无症状 DVT 后发生 PTS 的病因学因素的假设。 PTS 和 CPVD 影响着美国 250 万人； 20% 会出现严重的静脉溃疡疾病。由此造成的残疾估计每年损失 200 万个工作日，每年的医疗费用为 3 亿美元。这里的研究结果可以为开发治疗和预防 PTS 的新疗法奠定基础。