Association of Thrombophilia and Inflammation with Post-Thrombotic Syndrome

描述（申请人提供）： 深静脉血栓形成（DVT）或肺栓塞每年影响1-3/1000的成年人群，或每年近200，000人，发病率随年龄呈指数级上升。静脉血栓形成的负担主要涉及DVT，其在20- 50%的病例中并发血栓形成后综合征（PTS）。PTS的范围从轻度水肿到致残性症状性疾病，伴有营养性皮肤变化、慢性疼痛和静脉性皮肤溃疡。虽然PTS被认为是由于静脉瓣损伤导致的反流或慢性静脉阻塞限制流出而发生的，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，以评估慢性外周静脉疾病（CPVD）的分子决定因素，在多种族的一般人群样本，圣地亚哥人口研究（SDPS）。参与者进行了详细的体格检查和双功腿部超声检查，以根据解剖和临床结果确定是否存在CPVD。我们将讨论以下假设：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，通过多普勒超声评估的深功能性静脉疾病（DFD）和在不存在DFD的情况下发生的浅表静脉功能性疾病（SFD）的风险增加，并伴有PTS的临床特征。2.在具有反映不同方面炎症的生物标志物水平较高的参与者中，具有PTS特征的DFD或SFD的风险将增加。3.鉴于肥胖与CPVD和PTS风险的相关性，DFD或SFD的风险将增加，PTS的特征与反映脂肪细胞产物的生物标志物水平较高相关。为了检验这些假设，将在SDPS参与者（包括370例对照参与者和370例CPVD病例）的储存生物标本中测量表型和遗传分子生物标志物，重点是血栓后综合征。研究结果将允许形成关于临床诊断或临床无症状DVT后发生PTS的病因因素的假设。PTS和CPVD影响美国250万人; 20%的人发展为静脉溃疡的严重疾病。由此造成的残疾估计每年损失200万个工作日，医疗费用每年3亿美元。这些发现可以为开发治疗和预防PTS的新疗法奠定基础。

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.