title: Increased adhesive properties of neutrophils and inflammatory markers in venous thromboembolism patients with residual vein occlusion and high D-dimer levels.
abstract: BACKGROUND
  Venous thromboembolism (VTE) develops via a multicellular process on the endothelial surface. Although widely recognized, the relationship between inflammation and thrombosis, this relationship has been mostly explored in clinical studies by measuring circulating levels of inflammatory cytokines. However, the role of inflammatory cells, such as neutrophils, in the pathogenesis of VTE is not clear in humans.
  
  
  OBJECTIVE
  To evaluate the adhesive properties of neutrophils, erythrocytes and platelets in VTE patients and to correlate findings with inflammatory and hypercoagulability marker levels.
  
  
  METHODS
  Study group consisted of twenty-nine VTE patients and controls matched according to age, gender and ethnic background. Adhesive properties of neutrophils, erythrocytes and platelets were determined using a static adhesion assay. Neutrophil adhesion molecules expressions were evaluated by flow cytometry. Inflammatory and hypercoagulability marker levels were evaluated by standard methods. Residual vein occlusion (RVO) was evaluated by Doppler ultrasound.
  
  
  RESULTS
  No significant difference could be observed in platelet and erythrocyte adhesion between VTE patients and controls. Interestingly, VTE patients with high levels of D-dimer and RVO, demonstrated a significant increase in neutrophil adhesion, compared to controls and remaining patients. Inflammatory markers (IL-6, IL-8, TNF-α) were also significantly elevated in this subgroup, compared to other VTE patients. Adhesive properties of neutrophils correlated with IL-6 and D-dimer levels. Neutrophils adhesion molecules (CD11a, CD11b and CD18) were not altered in any of the groups.
  
  
  CONCLUSIONS
  These findings not only support the hypothesis of an association between inflammation and hypercoagulability, but more importantly, highlight the role of neutrophils in this process.
authors.affiliation: Hematology and Hemotherapy Center, University of Campinas - UNICAMP, São Paulo, Brazil. Electronic address: kiarazapponi@gmail.com.
authors.forename: Kiara C S
authors.initials: KC
authors.lastname: Zapponi
authors.affiliation: Hematology and Hemotherapy Center, University of Campinas - UNICAMP, São Paulo, Brazil.
authors.forename: Bruna M
authors.initials: BM
authors.lastname: Mazetto
authors.affiliation: Hematology and Hemotherapy Center, University of Campinas - UNICAMP, São Paulo, Brazil.
authors.forename: Luis F
authors.initials: LF
authors.lastname: Bittar
authors.affiliation: Hematology and Hemotherapy Center, University of Campinas - UNICAMP, São Paulo, Brazil.
authors.forename: Aline
authors.initials: A
authors.lastname: Barnabé
authors.affiliation: Hematology and Hemotherapy Center, University of Campinas - UNICAMP, São Paulo, Brazil.
authors.forename: Fernanda D
authors.initials: FD
authors.lastname: Santiago-Bassora
authors.affiliation: Department of Clinical Pathology, University of Campinas - UNICAMP, São Paulo, Brazil.
authors.forename: Erich V
authors.initials: EV
authors.lastname: De Paula
authors.affiliation: Hematology and Hemotherapy Center, University of Campinas - UNICAMP, São Paulo, Brazil.
authors.forename: Fernanda A
authors.initials: FA
authors.lastname: Orsi
authors.affiliation: Hematology and Hemotherapy Center, University of Campinas - UNICAMP, São Paulo, Brazil.
authors.forename: Carla F
authors.initials: CF
authors.lastname: Franco-Penteado
authors.affiliation: Hematology and Hemotherapy Center, University of Campinas - UNICAMP, São Paulo, Brazil.
authors.forename: Nicola
authors.initials: N
authors.lastname: Conran
authors.affiliation: Hematology and Hemotherapy Center, University of Campinas - UNICAMP, São Paulo, Brazil.
authors.forename: Joyce M
authors.initials: JM
authors.lastname: Annichino-Bizzacchi
mesh_terms: D000328:Adult; D000368:Aged; D015415:Biomarkers / Q000097:blood; D001792:Blood Platelets / Q000378:metabolism / Q000473:pathology; D016022:Case-Control Studies; D002448:Cell Adhesion / Q000502:physiology; D004912:Erythrocytes / Q000378:metabolism / Q000473:pathology; D005260:Female; D005338:Fibrin Fibrinogen Degradation Products / Q000378:metabolism*; D006801:Humans; D007249:Inflammation / Q000097:blood / Q000473:pathology; D015850:Interleukin-6 / Q000097:blood; D016209:Interleukin-8 / Q000097:blood; D008297:Male; D008875:Middle Aged; D009504:Neutrophils / Q000378:metabolism / Q000473:pathology*; D014409:Tumor Necrosis Factor-alpha / Q000097:blood; D054556:Venous Thromboembolism / Q000097:blood* / Q000473:pathology; D055815:Young Adult
chemical_list: D015415:Biomarkers; D005338:Fibrin Fibrinogen Degradation Products; C508600:IL6 protein, human; D015850:Interleukin-6; D016209:Interleukin-8; D014409:Tumor Necrosis Factor-alpha; C036309:fibrin fragment D
keywords: Cell adhesion; Erythrocytes; Inflammation; Neutrophils; Platelets; Venous thromboembolism