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. 2013 Oct 1;1(4):341-348.e1.
doi: 10.1016/j.jvsv.2012.12.002.

Plasma DNA is Elevated in Patients with Deep Vein Thrombosis

J A Diaz  1 , T A Fuchs  2 , T O Jackson  3 , J A Kremer Hovinga  4 , B Lämmle  5 , P K Henke, D D Myers Jr, D D Wagner, T W Wakefield; for the Michigan Research Venous Group*
Affiliations

Plasma DNA is Elevated in Patients with Deep Vein Thrombosis

J A Diaz et al. J Vasc Surg Venous Lymphat Disord. .

Abstract

Objective: 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.

Background: 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.

Setting: 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.

Methods: 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.

Results: 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).

Conclusions: 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.

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Figures

Figure 1
Figure 1
DVT Wells score.
Figure 2
Figure 2
Comparison of circulating DNA levels in patients. DVT (+): DVT positive group; DVT (−): DVT negative group; Control: Control group. Bars: represent ± standard error of the mean.
Figure 3
Figure 3
Logistic regression model of DNA values
Figure 4
Figure 4
ADAMTS13/VWF:activity (A) and ADAMTS13/VWF:Ag ratios (B) results. Control: Control group; DVT (−): DVT negative group; DVT (+): DVT positive group. Bars: represent ± standard error of the mean.
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