title: Tissue factor coagulation pathway and blood cells activation state in renal insufficiency.
abstract: BACKGROUND
  Atherosclerotic cardiovascular disease is the leading cause of the increased morbidity and mortality observed in uremic patients. Thrombosis is an important contributor to the evolution of atherosclerotic lesions. The physiologically-relevant blood clotting depends on binding of activated factor VII (FVIIa) to exposed tissue factor (TF) on activated/damaged cells.
  
  
  METHODS
  A cross-sectional study was performed on three age- and sex-matched groups of individuals: one group of 50 patients on maintenance hemodialysis (D group), one of 50 patients with a non-dialysed renal insufficiency (ND group) and one of 50 healthy controls (HC group). We studied basal plasma concentrations of FVIIa, factor VII-related antigen (FVIIAg), soluble TF, tissue factor pathway inhibitor (TFPI), TF-dependent circulating monocytes procoagulant activity (TF-dMPA), tissue factor-dependent plasma reactivity to activated protein C (TF-aPC), D-dimers (D-Di), and circulating markers of cellular activation/injury: soluble thrombomodulin (sTM), circulating microparticles (microP), soluble leukocyte, endothelial and platelet selectins (sL-selectin, sE-selectin, sP-selectin), soluble intercellular adhesion molecule 1 and vascular cell adhesion molecule 1 (sICAM-1 and sVCAM-1). Their variations induced, in hemodialysis patients, by a dialysis run were thereafter studied
  
  
  RESULTS
  Values of FVIIa, FVIIa/FVIIAg ratio, sTF, TFPI, TF-dMPA, D-Di, sTM, microP, sL, sE and sP selectins, sICAM-1 and sVCAM-1 increased all along the hierarchy HC group/ND group/D group. Microparticles were mainly of platelet origin, to a lesser extent of monocyte origin. Dialysis induced an increase of FVIIa, sTF, TF-dMPA and circulating markers of cellular activation/injury. Strong correlations were observed between FVIIa/FVIIAg ratio and serum creatinine levels, sTF, TF-dMPA, sTM, sE-selectin, sVCAM-1. The TF-aPC was impaired in the ND and the D group, and the lower values were, in the D group, associated with antecedents of vascular access thrombosis.
  
  
  CONCLUSIONS
  Renal insufficiency is associated to an activation of the tissue factor coagulation pathway, to a platelet, monocyte and endothelial activation/injury and to a deficient tissue-factor induced response to activated protein C which culminate in end-stage disease and are increased by hemodialysis runs. This contributes to linked coagulation and cellular conditions for an enhanced atherosclerosis progression. Due to the TF pathway activation, the therapeutic use of recombinant TFPI should be evaluated.
authors.affiliation: Laboratoire d'Hématologie, Centre Hospitalier Universitaire, Nîmes, France.
authors.forename: E
authors.initials: E
authors.lastname: Mercier
authors.forename: B
authors.initials: B
authors.lastname: Branger
authors.forename: F
authors.initials: F
authors.lastname: Vecina
authors.forename: B
authors.initials: B
authors.lastname: Al-Sabadani
authors.forename: J
authors.initials: J
authors.lastname: Berlan
authors.forename: M
authors.initials: M
authors.lastname: Dauzat
authors.forename: J
authors.initials: J
authors.lastname: Fourcade
authors.forename: J C
authors.initials: JC
authors.lastname: Gris
mesh_terms: D020016:Activated Protein C Resistance / Q000175:diagnosis / Q000209:etiology; D000328:Adult; D000368:Aged; D001777:Blood Coagulation / Q000502:physiology*; D001779:Blood Coagulation Factors / Q000378:metabolism; D016022:Case-Control Studies; D015815:Cell Adhesion Molecules / Q000097:blood; D003430:Cross-Sectional Studies; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D006435:Renal Dialysis / Q000009:adverse effects; D051437:Renal Insufficiency / Q000097:blood*; D019851:Thrombophilia / Q000097:blood / Q000209:etiology*; D013925:Thromboplastin / Q000378:metabolism*
chemical_list: D001779:Blood Coagulation Factors; D015815:Cell Adhesion Molecules; D013925:Thromboplastin