Does cell-free DNA promote coagulation and inhibit fibrinolysis in patients with unprovoked venous thromboembolism?

Cell-free DNA (CFDNA) is the major structural component of neutrophil extracellular traps (NETs). CFDNA contributes to the prothrombotic potential of NETs by promoting thrombin generation and inhibiting fibrinolysis. Patients with venous thromboembolism (VTE) have elevated circulating nucleosomes (i...

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Bibliographic Details
Published in:Thrombosis research 2020-02, Vol.186, p.13-19
Main Authors: Medeiros, Sarah K., Emery, Brittney, Bhagirath, Vinai, Parpia, Sameer, Dwivedi, Dhruva J., Dwivedi, Naviya J., Kearon, Clive, Liaw, Patricia C.
Format: Article
Language:English
Subjects:
Biomarker
Blood
Cell-free DNA
Coagulation
Fibrinolysis
Venous thromboembolism (VTE)
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Summary:Cell-free DNA (CFDNA) is the major structural component of neutrophil extracellular traps (NETs). CFDNA contributes to the prothrombotic potential of NETs by promoting thrombin generation and inhibiting fibrinolysis. Patients with venous thromboembolism (VTE) have elevated circulating nucleosomes (i.e. DNA-histone complexes). In this study, we investigated if CFDNA contributes to a procoagulant and an antifibrinolytic state in patients with unprovoked VTE. Plasma samples from patients with a first episode of unprovoked VTE were obtained from the D-Dimer Optimal Duration Study (DODS). We measured CFDNA plasma levels in 263 patients while on warfarin and 1-month after stopping. Thrombin generation assays and clot lysis assays were measured in patients after stopping warfarin. Comparisons were made with healthy controls. CFDNA levels in VTE patients who stopped warfarin (5.53 μg/mL; 95%CI: 5.34–5.72) were higher than during warfarin therapy (3.11 μg/mL; 95%CI: 2.98–3.25; p 
ISSN:0049-3848
1879-2472
DOI:10.1016/j.thromres.2019.11.030