Association of Thrombophilia and Inflammation with Post-Thrombotic Syndrome

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。

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.