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: 7071382
• 负责人: MARY CUSHMAN
• 金额: $ 35.62万
• 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/7071382
• 关键词: adipocytes; biomarker; blood coagulation disorders; cardiovascular disorder epidemiology; clinical research; disease /disorder etiology; genetic disorder; genetic susceptibility; human data; human tissue; inflammation; medical complication; patient oriented research; peripheral blood vessel disorder; thrombosis; venous thrombosis

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）： 深静脉血栓形成（DVT）或肺栓塞每年每年1-3人每年1-3，每年接近200,000，其发病率随着年龄的增长而呈指数增长。静脉血栓形成的负担主要涉及DVT，这在20-50％的病例中因血栓形成后综合征（PTS）而复杂。 PTS具有从轻度水肿到残疾症状性疾病的频谱，具有营养性皮肤变化，慢性疼痛和静脉皮肤溃疡。虽然PT被认为是由于对静脉瓣的损害而导致的，导致静脉反流或慢性静脉阻塞限制流出，但尚未对PT的其他病因决定因素进行广泛研究。我们提出了一项基于人群的研究，以评估多种族普通人群样本（圣地亚哥人口研究（SDPS））中慢性外周静脉疾病（CPVD）的分子决定因素。参与者进行了详细的体格检查和双链腿超声检查，以基于解剖和临床发现建立CPVD的存在。我们将解决以下假设：1。在与遗传性疾病的患者（“遗传性血栓形成型”）相关的人中，通过双层静脉疾病（DFD）的风险会增加，该疾病（DFD）通过双层超声和浅表静脉功能疾病（SFD）（SFD）评估时，它在不在DFD和DFD的情况下发生时会增加。 2。在反映较高的生物标志物的参与者中，DFD或SFD的风险会增加，反映出不同方面的炎症。 3。鉴于肥胖症与CPVD和PT的风险相关联，DFD或SFD的风险与PTS的特征以及反映脂肪细胞产物的更高水平的PTS的特征会增加。为了测试这些假设，将在SDPS参与者（包括370个对照参与者和370例CPVD）的SDPS参与者的储存生物样本中测量表型和遗传分子生物标志物，重点介绍了促进后综合征。发现将允许在临床诊断或临床沉默的DVT后，就PT的发展中形成有关病因学因素的假设。 PTS和CPVD影响美国250万人； 20％因静脉溃疡而患上严重疾病。结果估计，每年的工作日损失了200万美元，每年损失了3亿美元的医疗费用。这里的发现可以构成开发新疗法以治疗和预防的基础。