Plasma DNA is elevated in patients with deep vein thrombosis

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, known as extracellular traps (ETs), which have recently been linked to experimental DVT. In baboons and mice, extracellular DNA colocalized 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. Methods 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 nonpregnant volunteers without signs or symptoms of active or previous DVT (n = 19). Patients were excluded if they were younger than 18 years of age, unwilling to consent, pregnant, on an anticoagulant therapy, or diagnosed with isolated calf vein thrombosis. Blood was collected for circulating DNA, C-reactive protein, 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 activity and Ag was assessed. Results Our results showed that circulating DNA (a surrogate marker for neutrophil extracellular traps) was significantly elevated in DVT patients, compared with both DVT-negative patients (57.7 ± 6.3 vs 17.9 ± 3.5 ng/mL; P P P P P P P P Conclusions Plasma DNA is elevated in patients with DVT 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.