title: Plasma hypercoagulability in the presence of thrombomodulin but not of activated protein C in patients with cirrhosis.
abstract: OBJECTIVE
  Cirrhosis significantly changes all hemostasis steps. Recent studies suggest that cirrhosis is associated with a coagulopathy leading to a hypercoagulable state. The underlying mechanisms are not fully understood, but protein C deficiency is probably a major determinant of this phenotype. The aim of this study was to compare the results of thrombin generation assays performed with addition of thrombomodulin or activated protein C to assess the effect of by-passing the protein C activation step in cirrhotic patients and healthy controls.
  
  
  METHODS
  Fifty-eight patients with cirrhosis and 26 healthy controls were prospectively included in this study. Thrombin generation was determined in platelet-poor plasma using 5 pM of tissue factor and 4 nM of phospholipids, without and with external addition of 1 nM thrombomodulin or 4 nM activated protein C. All results were normalized with the values of a pool of normal plasma samples to limit inter-plate variability.
  
  
  RESULTS
  When thrombin generation assays were performed in the presence of thrombomodulin, endogenous thrombin potential (ETP) and ETP with/ETP without TM ratio were significantly higher in cirrhotic patients than in healthy controls (P < 0.0001). Moreover, these values progressively increased with cirrhosis severity. When thrombin generation assays were performed with activated protein C, all thrombin generation parameters were comparable between healthy controls and cirrhotic patients, despite an acquired protein S deficiency.
  
  
  CONCLUSIONS
  In the presence of activated protein C, no hypercoagulability was observed, adding to the current evidence that acquired protein C deficiency plays a key role in the coagulation imbalance.
authors.affiliation: CHU Clermont-Ferrand, Service d'Hématologie Biologique, Clermont-Ferrand, France.|INRA-Université d'Auvergne, UMR1019, Unité de nutrition humaine, Clermont-Ferrand, France.
authors.forename: Aurélien
authors.initials: A
authors.lastname: Lebreton
authors.affiliation: CHU Clermont-Ferrand, Service d'Hématologie Biologique, Clermont-Ferrand, France.|INRA-Université d'Auvergne, UMR1019, Unité de nutrition humaine, Clermont-Ferrand, France.
authors.forename: Thomas
authors.initials: T
authors.lastname: Sinegre
authors.affiliation: CHU Clermont-Ferrand, Unité de Biostatistiques (Direction de la Recherche Clinique et de L'innovation), Clermont-Ferrand, France.
authors.forename: Bruno
authors.initials: B
authors.lastname: Pereira
authors.affiliation: CHU Clermont-Ferrand, Service d'Hépato-Gastro-Entérologie, Clermont-Ferrand, France.
authors.forename: Géraldine
authors.initials: G
authors.lastname: Lamblin
authors.affiliation: CHU Clermont-Ferrand, Service d'Hépato-Gastro-Entérologie, Clermont-Ferrand, France.|Université d'Auvergne, UMR CNRS 6284, Clermont-Ferrand, France.
authors.forename: Cédric
authors.initials: C
authors.lastname: Duron
authors.affiliation: CHU Clermont-Ferrand, Service d'Hépato-Gastro-Entérologie, Clermont-Ferrand, France.|Université d'Auvergne, UMR CNRS 6284, Clermont-Ferrand, France.
authors.forename: Armand
authors.initials: A
authors.lastname: Abergel
mesh_terms: D000328:Adult; D000368:Aged; D001777:Blood Coagulation; D005260:Female; D006801:Humans; D008103:Liver Cirrhosis / Q000097:blood* / Q000150:complications*; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D011486:Protein C / Q000378:metabolism*; D020151:Protein C Deficiency / Q000150:complications*; D012720:Severity of Illness Index; D018180:Thrombomodulin / Q000378:metabolism*; D019851:Thrombophilia / Q000209:etiology*; D055815:Young Adult
chemical_list: D011486:Protein C; D018180:Thrombomodulin
keywords: activated protein C; cirrhosis; hypercoagulability; thrombin generation; thrombomodulin