Circulating extracellular DNA is an independent predictor of mortality in elderly patients with venous thromboembolism

PLoS One. 2018 Feb 23;13(2):e0191150. doi: 10.1371/journal.pone.0191150. eCollection 2018.

Abstract

Background: Venous thromboembolism (VTE) is a major cause of morbidity and mortality in elderly patients. Extracellular DNA is a pro-inflammatory and pro-thrombotic mediator in vitro and in animal models. Levels of circulating extracellular DNA (ceDNA) are increased in VTE patients, but the association of ceDNA with VTE extent and clinical outcome is poorly understood.

Objectives: We analyzed the association of ceDNA with the extent of VTE, categorized as distal and proximal deep vein thrombosis and pulmonary embolism, and with the clinical outcomes VTE recurrence and mortality.

Methods: We quantified ceDNA by a fluorescent probe, as well as circulating nucleosomes and neutrophil extracellular traps (NETs) by ELISA in plasma from 611 patients aged ≥ 65 years with acute VTE of a prospective cohort study (SWITCO65+).

Results: Levels of ceDNA and nucleosomes, but not NETs, correlated with VTE extent. Infectious comorbidities independently increased ceDNA levels in VTE. CeDNA strongly correlated with C-reactive protein and leukocytosis, suggesting an association of ceDNA with inflammation in VTE patients. CeDNA furthermore predicted PE-related and all-cause mortality, but not VTE recurrence, during a 3-year follow-up.

Conclusions: Our study suggests that ceDNA levels in VTE patients reflect the degree of inflammation and may serve as a biomarker to stratify VTE patients at risk for mortality.

Publication types

  • Multicenter Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Aged, 80 and over
  • Biomarkers / blood
  • C-Reactive Protein / metabolism
  • Cohort Studies
  • DNA / blood*
  • Extracellular Fluid / metabolism
  • Extracellular Traps / metabolism
  • Female
  • Humans
  • Inflammation Mediators / blood
  • Male
  • Nucleosomes / metabolism
  • Prospective Studies
  • Pulmonary Embolism / blood
  • Pulmonary Embolism / mortality
  • Recurrence
  • Risk Factors
  • Switzerland / epidemiology
  • Venous Thromboembolism / blood*
  • Venous Thromboembolism / mortality
  • Venous Thrombosis / blood
  • Venous Thrombosis / mortality

Substances

  • Biomarkers
  • Inflammation Mediators
  • Nucleosomes
  • C-Reactive Protein
  • DNA

Grants and funding

This cohort study was supported by the Swiss National Science Foundation (grant 33CSCO-122659/139470). The funding agency had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication. This research was supported by a Marie Curie Fellowship (PIIF-GA-2013-628264) and funding from the “Stiftung für Pathobiochemie und Molekulare Diagnostik” of the German Society for Clinical Chemistry and Laboratory Medicine to T.A.F. and by Hjärt Lungfonden (20140741), Cancerfonden (CAN 2016/612), Vetenskapsrådet (K2013-65X-21462-04-5), German Research Society (SFB841, TP B8; SFB877 TP A11), and an European Research Council grant (ERC-StG-2012-311575_F-12) to T.R.. B.L. was supported by the German Federal Ministry of Education and Research (BMBF 01EO1503). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.