Plasma DNA is Elevated in Patients with Deep Vein Thrombosis.
Plasma DNA is Elevated in Patients with Deep Vein Thrombosis.
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DOI：
10.1016/j.jvsv.2012.12.002
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发表时间：
2013-10-01
期刊：
影响因子：
--
通讯作者：
Wakefield, T W
中科院分区：
文献类型：
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作者：
Diaz, J A;Fuchs, T A;Jackson, T O;Kremer Hovinga, J A;Lammle, B;Henke, P K;Myers, D D Jr;Wagner, D D;Wakefield, T W
研究深静脉血栓形成（DVT）患者血浆DNA是否升高，并确定是否与DVT的其他生物标志物相关。白细胞释放DNA以形成细胞外陷阱（extracellular trap，ETP），最近被认为与实验性DVT有关。在狒狒和小鼠中，细胞外DNA与血管性血友病因子（VWF）在血栓中共定位，并且在血栓形成时DNA出现在循环中。血栓与临床DVT无关。从2008年12月至2010年8月，患者通过密歇根大学诊断血管单位进行筛选，并分为三个不同的组：1）DVT阳性组，包括DVT症状的患者，其通过压缩多普勒超声证实（n=47）; 2）DVT阴性组，包括表现为肿胀和腿部疼痛但压缩多普勒超声阴性的患者（n=28）;和3）没有活动性或先前DVT的体征或症状的健康非妊娠志愿者的对照组（n=19）。如果患者年龄小于18岁、不愿意同意、怀孕、接受抗凝治疗或诊断为孤立性小腿静脉血栓形成，则将其排除。收集血液用于循环DNA、CRP、D-二聚体、VWF活性、髓过氧化物酶（MPO）、ADAMTS 13和VWF。评估患者DVT风险的威尔斯评分。生成受试者工作特征（ROC）曲线，以确定循环DNA水平与DVT存在之间的关系强度。进行斯皮尔曼相关性以确定DNA水平和生物标志物与威尔斯评分之间的关系。此外，还评估了ADAMTS 13/VWF的比值。我们的结果显示，DVT患者的循环DNA（NET的替代标记物）显著升高，与DVT阴性患者（57.7±6.3 vs. 17.9±3.5ng/mL，P<0.01）和对照组（57.7±6.3 vs. 23.9±2.1ng/mL，P<0.01）相比。与CRP（P<0.01）、D-二聚体（P<0.01）、VWF（P<0.01）、威尔斯评分（P<0.01）和髓过氧化物酶（MPO）（P<0.01）呈强正相关，与ADAMTS 13（P<0.01）和ADAMTS 13/VWF比值呈沿着强负相关。Logistic回归模型显示血浆DNA与DVT的存在有很强的相关性（ROC曲线确定为0.814）。血浆DNA在深静脉血栓形成患者中升高，并与DVT的生物标志物相关。循环DNA和MPO之间的强相关性表明，中性粒细胞可能是DVT患者血浆DNA的来源。
To investigate if plasma DNA is elevated in patients with deep vein thrombosis (DVT) and to determine whether there is a correlation with other biomarkers of DVT. Leukocytes release DNA to form extracellular traps (ETs), which have recently been linked to experimental DVT. In baboons and mice, extracellular DNA co-localized with von Willebrand factor (VWF) in the thrombus and DNA appeared in circulation at the time of thrombus formation. ETs have not been associated with clinical DVT. From December 2008 to August 2010, patients were screened through the University of Michigan Diagnostic Vascular Unit and were divided into three distinct groups: 1) the DVT positive group, consisting of patients who were symptomatic for DVT, which was confirmed by compression duplex ultrasound (n=47); 2) the DVT negative group, consisting of patients that present with swelling and leg pain but had a negative compression duplex ultrasound, (n=28); and 3) a control group of healthy non-pregnant volunteers without signs or symptoms of active or previous DVT (n=19). Patients were excluded if they were less than 18 years of age, unwillingness to consent, pregnant, on an anticoagulant therapy, or diagnosed with isolated calf vein thrombosis. Blood was collected for circulating DNA, CRP, D-dimer, VWF activity, myeloperoxidase (MPO), ADAMTS13 and VWF. The Wells score for a patient’s risk of DVT was assessed. The Receiver Operating Characteristic (ROC) curve was generated to determine the strength of the relationship between circulating DNA levels and the presence of DVT. A Spearman correlation was performed to determine the relationship between the DNA levels and the biomarkers and the Wells score. Additionally the ratio of ADAMTS13/VWF was assessed. Our results showed that circulating DNA (a surrogate marker for NETs) was significantly elevated in DVT patients, compared to both DVT negative patients (57.7±6.3 vs. 17.9±3.5ng/mL, P<.01) and controls (57.7±6.3 vs. 23.9±2.1ng/mL, P<.01). There was a strong positive correlation with CRP (P<.01), D-dimer (P<.01), VWF (P<.01), Wells score (P<.01) and myeloperoxidase (MPO) (P<.01), along with a strong negative correlation with ADAMTS13 (P<.01) and the ADAMTS13/VWF ratio. The logistic regression model showed a strong association between plasma DNA and the presence of DVT (ROC curve was determined to be 0.814). Plasma DNA is elevated in patients with deep vein thrombosis and correlates with biomarkers of DVT. A strong correlation between circulating DNA and MPO suggests that neutrophils may be a source of plasma DNA in patients with DVT.