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

Jiménez-Alcázar, Miguel; Limacher, Andreas; Panda, Rachita; Méan, Marie; Bitterling, Josephine; Peine, Sven; Renné, Thomas; Beer, Jürg H; Aujesky, Drahomir; Lämmle, Bernhard; Fuchs, Tobias A (2018). Circulating extracellular DNA is an independent predictor of mortality in elderly patients with venous thromboembolism. PLoS ONE, 13(2), e0191150. Public Library of Science 10.1371/journal.pone.0191150

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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.

Item Type:

Journal Article (Original Article)

Division/Institute:

04 Faculty of Medicine > Department of Haematology, Oncology, Infectious Diseases, Laboratory Medicine and Hospital Pharmacy (DOLS) > Clinic of Haematology and Central Haematological Laboratory
04 Faculty of Medicine > Department of General Internal Medicine (DAIM) > Clinic of General Internal Medicine
04 Faculty of Medicine > Department of General Internal Medicine (DAIM) > Clinic of General Internal Medicine > Centre of Competence for General Internal Medicine
04 Faculty of Medicine > Pre-clinic Human Medicine > Institute of Social and Preventive Medicine
04 Faculty of Medicine > Pre-clinic Human Medicine > CTU Bern

UniBE Contributor:

Limacher, Andreas; Méan Pascual, Marie; Aujesky, Drahomir and Lämmle, Bernhard

Subjects:

600 Technology > 610 Medicine & health
300 Social sciences, sociology & anthropology > 360 Social problems & social services

ISSN:

1932-6203

Publisher:

Public Library of Science

Language:

English

Submitter:

Christine Baumgartner

Date Deposited:

17 Jan 2019 19:06

Last Modified:

05 Jul 2019 09:12

Publisher DOI:

10.1371/journal.pone.0191150

PubMed ID:

29474368

Additional Information:

Jimenez and Limacher contributed equally to this work.

BORIS DOI:

10.7892/boris.123177

URI:

https://boris.unibe.ch/id/eprint/123177

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