title: Long-term increased factor VIII levels are associated to interleukin-6 levels but not to post-thrombotic syndrome in patients with deep venous thrombosis.
abstract: BACKGROUND
  Increased FVIII levels are a well established risk factor for deep venous thrombosis (DVT), whose etiopathogenesis is not yet well understood. In this study, we aimed to evaluate the possibility that inflammatory markers and post-thrombotic syndrome (PTS) could contribute to FVIII levels in patients with a history of DVT.
  
  
  METHODS
  It is a case-control study that included 68 patients with DVT of the lower limbs 32 months after the acute episode, and 67 healthy adults as controls. We evaluated plasma levels of FVIII, VWF, D-dimer and serum levels of CRP, IL-6, IL-8, TNF-α in patients and controls. The presence of PTS was evaluated by the Villalta scale.
  
  
  RESULTS
  Patients with DVT presented higher levels of FVIII, VWF and D-dimer when compared to controls (P ≤ 0.001). Almost 50% of patients presented FVIII levels above 90th percentile. Furthermore, IL-6 (1.19 vs. 0.98 pg/mL, P = 0.01) and TNF-α (2.27 vs. 1.57 pg/mL, P ≤ 0.001) were also higher in patients when compared to controls. In a linear regression multivariate model, VWF and IL-6 levels were independent factors associated with FVIII levels (P ≤ 0.001). FVIII levels were not increased in patients with PTS. Patients with PTS showed higher levels of IL-8 when compared to patients without PTS (23.03 vs. 18.20 pg/mL, P = 0.04).
  
  
  CONCLUSIONS
  In conclusion, we demonstrated that DVT is associated with increased levels of inflammatory and coagulation markers, including FVIII, even a long time after the acute episode. Moreover, IL-6 levels were an independent factor associated with FVIII levels. Finally, PTS seems to be related to inflammatory cytokine IL-8, a proinflammatory and proangiogenic chemokine, but not to FVIII levels.
authors.affiliation: Hematology and Hemotherapy Center, University of Campinas, Campinas, SP, Brazil. Electronic address: lfbsckayer@hotmail.com.
authors.forename: Luis Fernando
authors.initials: LF
authors.lastname: Bittar
authors.affiliation: Hematology and Hemotherapy Center, University of Campinas, Campinas, SP, Brazil.
authors.forename: Bruna de Moraes
authors.initials: Bde M
authors.lastname: Mazetto
authors.affiliation: Hematology and Hemotherapy Center, University of Campinas, Campinas, SP, Brazil.
authors.forename: Fernanda L Andrade
authors.initials: FL
authors.lastname: Orsi
authors.affiliation: Hematology and Hemotherapy Center, University of Campinas, Campinas, SP, Brazil.
authors.forename: Marina P
authors.initials: MP
authors.lastname: Collela
authors.affiliation: Hematology and Hemotherapy Center, University of Campinas, Campinas, SP, Brazil.
authors.forename: Erich Vinícius
authors.initials: EV
authors.lastname: De Paula
authors.affiliation: Hematology and Hemotherapy Center, University of Campinas, Campinas, SP, Brazil.
authors.forename: Joyce M
authors.initials: JM
authors.lastname: Annichino-Bizzacchi
mesh_terms: D000328:Adult; D016022:Case-Control Studies; D005169:Factor VIII / Q000032:analysis*; D005260:Female; D006801:Humans; D015850:Interleukin-6 / Q000097:blood*; D008297:Male; D008875:Middle Aged; D054070:Postthrombotic Syndrome / Q000097:blood* / Q000150:complications / Q000175:diagnosis; D020246:Venous Thrombosis / Q000097:blood* / Q000150:complications / Q000175:diagnosis; D014841:von Willebrand Factor / Q000032:analysis*
chemical_list: D015850:Interleukin-6; D014841:von Willebrand Factor; D005169:Factor VIII
keywords: Deep venous thrombosis; Factor VIII; Inflammation; Post-thrombotic syndrome; Von Willebrand factor