title: Circulating nucleosomes and neutrophil activation as risk factors for deep vein thrombosis.
abstract: OBJECTIVE
  The formation of neutrophil extracellular traps and the exposure of nucleosomes on these neutrophil extracellular traps contribute to coagulation activation and the propagation of deep vein thrombosis (DVT) in animal models. However, no data are available on the role of neutrophil extracellular traps or nucleosomes in patients with thrombosis.
  
  
  RESULTS
  We conducted a case-control study, in which levels of circulating nucleosomes and neutrophil elastase-α1-antitrypsin complexes were assessed in plasma from 150 patients with objectified symptomatic DVT (cases) and compared with 195 patients with a clinical suspicion of DVT but in whom DVT was excluded (controls). We explored the association between both nucleosomes and elastase-α1-antitrypsin complexes, and the presence of DVT by calculating the odds ratio with corresponding 95% CIs. Elevated levels of both circulating nucleosomes and elastase-α1-antitrypsin complexes were associated with a 3-fold risk of DVT, and the associations remained similar after adjustment for potential confounders (malignancy, smoking, recent immobilization, recent hospitalization). The risk increased with higher nucleosome and elastase-α1-antitrypsin complex levels, suggesting a dose-dependent relationship among circulating nucleosomes, activated neutrophils, and DVT.
  
  
  CONCLUSIONS
  Our study suggests an association among circulating nucleosomes, activated neutrophils, and presence of DVT in humans, which might have implications for treatment and prevention.
authors.affiliation: Department of Experimental Vascular Medicine, Academic Medical Center, University of Amsterdam, Amsterdam, the Netherlands.
authors.forename: Maurits L
authors.initials: ML
authors.lastname: van Montfoort
authors.forename: Femke
authors.initials: F
authors.lastname: Stephan
authors.forename: Mandy N
authors.initials: MN
authors.lastname: Lauw
authors.forename: Barbara A
authors.initials: BA
authors.lastname: Hutten
authors.forename: Gerard J
authors.initials: GJ
authors.lastname: Van Mierlo
authors.forename: Shabnam
authors.initials: S
authors.lastname: Solati
authors.forename: Saskia
authors.initials: S
authors.lastname: Middeldorp
authors.forename: Joost C M
authors.initials: JC
authors.lastname: Meijers
authors.forename: Sacha
authors.initials: S
authors.lastname: Zeerleder
mesh_terms: D000328:Adult; D015415:Biomarkers / Q000097:blood; D016022:Case-Control Studies; D005260:Female; D006801:Humans; D019272:Leukocyte Elastase / Q000097:blood; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D018375:Neutrophil Activation; D009504:Neutrophils / Q000201:enzymology / Q000276:immunology*; D009707:Nucleosomes / Q000378:metabolism*; D016017:Odds Ratio; D018570:Risk Assessment; D012307:Risk Factors; D015854:Up-Regulation; D020246:Venous Thrombosis / Q000097:blood / Q000175:diagnosis / Q000209:etiology* / Q000276:immunology; D000515:alpha 1-Antitrypsin / Q000097:blood
chemical_list: D015415:Biomarkers; D009707:Nucleosomes; D000515:alpha 1-Antitrypsin; C037741:alpha 1-antitrypsin-leukocyte elastase complex; D019272:Leukocyte Elastase