title: Cirrhosis patients have a coagulopathy that is associated with decreased clot formation capacity.
abstract: BACKGROUND
  The coagulopathy in cirrhosis is associated with thrombosis and bleeding.
  
  
  OBJECTIVE
  To gain better insights into the coagulopathy in patients with cirrhosis, we evaluated plasma thrombin generation and whole blood clot formation in a cross-sectional study.
  
  
  METHODS
  Blood was collected from 73 patients with all-cause cirrhosis (Child-Pugh-A n = 52, B n = 15, C n = 6) and 20 healthy controls. Activity of the coagulation pathways was measured with assays for factor (F) VIIa and FIXa-antithrombin and FXa-antithrombin complexes, respectively. Thrombin generation by calibrated automated thrombography was determined in platelet-poor plasma using a 1 or 5 pm tissue factor trigger with/without thrombomodulin. ROTEM measurements were performed in whole blood triggered with 35 pm tissue factor without/with 175 ng mL(-1) tissue plasminogen activator (the latter refered to as 'tPA-ROTEM').
  
  
  RESULTS
  We observed an increased generation of FVIIa and a moderately elevated amount of FIXa (in complex with antithrombin) without apparent increase in FX activation in patients with cirrhosis. In accordance with this prothrombotic state, markers of thrombin generation potential were also increased upon increasing severity of cirrhosis. In the whole blood clotting assay we observed delayed clot formation and decreased clot strength associated with increased severity of cirrhosis. No significant differences were found for tPA-ROTEM parameters of clot degradation.
  
  
  CONCLUSIONS
  These results indicate that cirrhosis patients have an overall procoagulant plasma milieu but a decreased whole blood clot formation capacity with an apparently unaltered resistance to clot lysis.
authors.affiliation: Laboratory for Clinical Thrombosis and Hemostasis, Department of Internal Medicine, Cardiovascular Research Institute Maastricht, Maastricht University Medical Center, Maastricht, the Netherlands.
authors.forename: M-C
authors.initials: MC
authors.lastname: Kleinegris
authors.forename: M H A
authors.initials: MH
authors.lastname: Bos
authors.forename: M
authors.initials: M
authors.lastname: Roest
authors.forename: Y
authors.initials: Y
authors.lastname: Henskens
authors.forename: A
authors.initials: A
authors.lastname: Ten Cate-Hoek
authors.forename: C
authors.initials: C
authors.lastname: Van Deursen
authors.forename: H M H
authors.initials: HM
authors.lastname: Spronk
authors.forename: P H
authors.initials: PH
authors.lastname: Reitsma
authors.forename: P G
authors.initials: PG
authors.lastname: De Groot
authors.forename: H
authors.initials: H
authors.lastname: Ten Cate
authors.forename: G
authors.initials: G
authors.lastname: Koek
mesh_terms: D000328:Adult; D000368:Aged; D001331:Automation; D001777:Blood Coagulation; D001778:Blood Coagulation Disorders / Q000150:complications*; D001792:Blood Platelets / Q000378:metabolism; D002138:Calibration; D016022:Case-Control Studies; D003430:Cross-Sectional Studies; D015949:Factor IXa / Q000737:chemistry; D015942:Factor VIIa / Q000737:chemistry; D005170:Factor X / Q000737:chemistry; D005260:Female; D005342:Fibrinolysis; D005355:Fibrosis / Q000150:complications*; D006801:Humans; D008297:Male; D008875:Middle Aged; D013916:Thrombelastography; D013917:Thrombin / Q000737:chemistry; D010959:Tissue Plasminogen Activator / Q000378:metabolism; D055815:Young Adult
chemical_list: D005170:Factor X; D015942:Factor VIIa; D015949:Factor IXa; D013917:Thrombin; D010959:Tissue Plasminogen Activator
keywords: cirrhosis; hemostasis; hypercoagulability; thrombin; thromboelastometry