title: Thrombin generation measured as thrombin-antithrombin complexes predicts clinical outcomes in patients with cirrhosis.
abstract: OBJECTIVE
  Hypercoagulability has been detected in patients with cirrhosis yet its clinical significance remains unclear. We investigated the association of hypercoagulability with clinical outcomes in patients with cirrhosis.
  
  
  METHODS
  Thrombin-antithrombin (TAT) complexes as thrombin generation (TG) marker, D-dimer, antithrombin (AT), protein C, protein S, international normalized ratio (INR), activated partial thromboplastin time, fibrinogen, Child-Pugh class and Model for End-Stage Liver Disease (MELD) were evaluated. Two different multivariate analyses were performed: one not including MELD (model 1) and one including MELD and excluding INR (model 2).
  
  
  RESULTS
  Eighty-one patients (Child-Pugh class A/B/C: 27/27/27) and 40 healthy subjects were enrolled. Only ΤΑΤ and AT were independently associated with increasing liver disease severity. Increased TAT levels and MELD score were significantly associated with ascites and varices at baseline. Independent predictors of follow-up events were: TAT and MELD score for new-onset ascites; TAT and AT for variceal bleeding (VB); TAT and AT for portal vein thrombosis (PVT); and TAT and MELD for mortality. TAT equaled MELD in mortality prediction at 12 and 18 months. TAT cut-offs at 5.35, 14.6, 13.5 and 9.25 ng/mL identified patient groups with significantly higher probability of new-onset ascites, VB, PVT and mortality, respectively.
  
  
  CONCLUSIONS
  Increased TG is strongly correlated with portal hypertension-related complications, PVT and mortality in patients with cirrhosis. Measuring TG by TAT could enable risk stratification and institution of preventive strategies to improve clinical outcomes.
authors.affiliation: 1st Division of Internal Medicine, Medical School.
authors.forename: Georgios N
authors.initials: GN
authors.lastname: Kalambokis
authors.affiliation: Hematology Laboratory Unit of Molecular Biology, Medical School.
authors.forename: Aikaterini
authors.initials: A
authors.lastname: Oikonomou
authors.affiliation: Division of Gastroenterology, Medical School, University of Ioannina, Ioannina, Greece.
authors.forename: Gerasimos
authors.initials: G
authors.lastname: Baltayiannis
authors.affiliation: 1st Division of Internal Medicine, Medical School.
authors.forename: Leonidas
authors.initials: L
authors.lastname: Christou
authors.affiliation: Hematology Laboratory Unit of Molecular Biology, Medical School.
authors.forename: Nikolaos I
authors.initials: NI
authors.lastname: Kolaitis
authors.affiliation: 1st Division of Internal Medicine, Medical School.|Division of Gastroenterology, Medical School, University of Ioannina, Ioannina, Greece.
authors.forename: Epameinondas V
authors.initials: EV
authors.lastname: Tsianos
keywords: cirrhosis; clinical outcome; thrombin generation; thrombin-antithrombin complexes