Association of Thrombophilia and Inflammation with Post-Thrombotic Syndrome

描述(由申请人提供)： 深静脉血栓形成(DVT)或肺血栓每年影响成人人口的1-3/1000，或每年近200,000，其发病率随着年龄呈指数上升。静脉血栓形成的负担主要涉及DVT，其中20%-50%的病例合并血栓后综合征(PTS)。PTS有一系列疾病，从轻微的浮肿到伴随营养皮肤变化、慢性疼痛和静脉性皮肤溃疡的致残症状性疾病。虽然PTS的发生被认为是由于静脉瓣膜受损而导致的返流或慢性静脉阻塞限制了流出，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，以评估多种族普通人群样本中慢性周围静脉疾病(CPVD)的分子决定因素，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，以根据解剖和临床结果确定是否存在CPVD。我们将提出以下假设：1.在与高凝状态相关的遗传性疾病(“遗传性血栓形成症”)患者中，当深静脉功能疾病(DFD)和浅表静脉功能疾病(SFD)在没有DFD的情况下并伴有PTS的临床特征时，其双功能超声评估的风险将增加。2.在反映不同方面炎症的生物标志物水平较高的参与者中，发生具有PTS特征的DFD或SFD的风险将增加。3.考虑到肥胖与CPVD和PTS的风险相关，DFD或SFD的风险将增加，伴随PTS特征的DFD或SFD的风险将随着反映脂肪细胞产物的生物标志物水平的提高而增加。为了验证这些假设，将在SDPS参与者的储存生物样本中测量表型和遗传分子生物标记物，其中包括370名对照参与者和370例CPVD病例，重点是血栓后综合征。这些发现将允许在临床诊断或临床无症状的DVT后形成关于PTS发生的病因的假说。在美国，PTS和CPVD影响着250万人；20%的人会患上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，医疗费用为3亿美元。这里的发现可以为开发治疗PTS的新疗法奠定基础，而且还可以预防PTS。

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.