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

Authors
  • Medeiros, Sarah K1
  • Emery, Brittney1
  • Bhagirath, Vinai2
  • Parpia, Sameer3
  • Dwivedi, Dhruva J2
  • Dwivedi, Naviya J1
  • Kearon, Clive2
  • Liaw, Patricia C4
  • 1 Thrombosis and Atherosclerosis Research Institute (TaARI), McMaster University, Hamilton, Ontario, Canada. , (Canada)
  • 2 Thrombosis and Atherosclerosis Research Institute (TaARI), McMaster University, Hamilton, Ontario, Canada; Department of Medicine, McMaster University, Hamilton, Ontario, Canada. , (Canada)
  • 3 Department of Oncology, McMaster University, Hamilton, Ontario, Canada. , (Canada)
  • 4 Thrombosis and Atherosclerosis Research Institute (TaARI), McMaster University, Hamilton, Ontario, Canada; Department of Medicine, McMaster University, Hamilton, Ontario, Canada. Electronic address: [email protected] , (Canada)
Type
Published Article
Journal
Thrombosis research
Publication Date
Nov 30, 2019
Volume
186
Pages
13–19
Identifiers
DOI: 10.1016/j.thromres.2019.11.030
PMID: 31838139
Source
Medline
Keywords
Language
English
License
Unknown

Abstract

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 < .001), and higher than in healthy controls (2.77 μg/mL; 95%CI: 2.42-3.11; p < .001). VTE patients had a procoagulant state as evidenced by a shorter lag time (30.8 min; 95%CI: 29.2-32.4) compared to controls (48.2 min; 95%CI :41.0-55.5; p < .001) and a greater endogenous thrombin potential (2656 nM∗min; 95%CI: 2479-2836) compared to healthy controls (1198 nM ∗ min; 95%CI: 793-1603). There was a higher proportion of clots generated from patient plasma that were resistant to lysis (43.7%) compared to healthy controls (46.3%; p < .05). CFDNA levels were not associated with enhanced thrombin generation or impaired fibrinolysis in VTE patients. CFDNA levels are elevated in patients with unprovoked VTE but do not correlate with the procoagulant or anti-fibrinolytic properties of patient plasma. This study suggests that additional factors in addition to CFDNA may contribute to the pathogenesis of VTE. Copyright © 2019 Elsevier Ltd. All rights reserved.

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