Circulating extracellular DNA is an independent predictor of mortality in elderly patients with venous thromboembolism.
- Jiménez-Alcázar M Institute of Clinical Chemistry and Laboratory Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
- Limacher A CTU Bern, and Institute of Social and Preventive Medicine, University of Bern, Bern, Switzerland.
- Panda R Institute of Clinical Chemistry and Laboratory Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
- Méan M Division of General Internal Medicine, University Hospital of Bern and University of Bern, Bern, Switzerland.
- Bitterling J Institute of Clinical Chemistry and Laboratory Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
- Peine S Institute of Transfusion Medicine, University Hospital Hamburg-Eppendorf, Hamburg, Germany.
- Renné T Institute of Clinical Chemistry and Laboratory Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
- Beer JH Cantonal Hospital of Baden, Baden, and Molecular Cardiology, University Hospital of Zürich, Zürich, Switzerland.
- Aujesky D Division of General Internal Medicine, University Hospital of Bern and University of Bern, Bern, Switzerland.
- Lämmle B Department of Hematology, University Hospital Bern and University of Bern, Bern, Switzerland.
- Fuchs TA Institute of Clinical Chemistry and Laboratory Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
- 2018-02-24
Published in:
- PloS one. - 2018
Aged
Aged, 80 and over
Biomarkers
C-Reactive Protein
Cohort Studies
DNA
Extracellular Fluid
Extracellular Traps
Female
Humans
Inflammation Mediators
Male
Nucleosomes
Prospective Studies
Pulmonary Embolism
Recurrence
Risk Factors
Switzerland
Venous Thromboembolism
Venous Thrombosis
English
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.
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.
- Language
-
- English
- Open access status
- gold
- Identifiers
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- DOI 10.1371/journal.pone.0191150
- PMID 29474368
- Persistent URL
- https://sonar.ch/global/documents/185113
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