title: Prominent protein Z-induced thrombin inhibition in cirrhosis: a new functional assay for hypercoagulability assessment.
abstract: OBJECTIVE
  Protein Z (PZ) is an anticoagulant that accelerates the inhibitory effect of PZ-dependent protease inhibitor (ZPI) on coagulation factor Xa. We assessed functional status of PZ system in 158 patients with liver cirrhosis and 59 healthy controls.
  
  
  METHODS
  Plasma PZ and ZPI levels were measured by enzyme immunoassay. Thrombin generation assays (TGA) were performed with and without thrombomodulin (TM) or PZ, and the ratios were calculated by dividing TGA values with TM or PZ by values without TM or PZ.
  
  
  RESULTS
  PZ and ZPI levels were reduced and elevated in advanced cirrhosis, respectively. The lag time ratio-PZ was significantly higher in cirrhosis patients than controls and correlated with the model for end-stage liver disease score. The peak thrombin ratio-PZ and endogenous thrombin potential (ETP) ratio-PZ were significantly lower in cirrhosis patients than controls and correlated with the severity of liver cirrhosis. The peak thrombin ratio-PZ was dramatically reduced in advanced cirrhosis. Cirrhosis patients had a significantly higher ETP ratio-TM than the controls, although the ratio was not correlated with cirrhosis severity. The lag time ratio-PZ and peak time ratio-PZ were significantly correlated with the levels of all coagulation and anticoagulation factors. Interestingly, the lag time ratio-PZ and peak thrombin ratio-PZ were significantly associated with thrombotic events.
  
  
  CONCLUSIONS
  The anticoagulant role of PZ is insufficient in advanced stages of cirrhosis. Our newly developed functional assay for measuring the PZ system is expected to reflect the ongoing hypercoagulability of cirrhosis.
authors.affiliation: Department of Laboratory Medicine, Seoul National University College of Medicine, Seoul, Korea.
authors.forename: Seon Young
authors.initials: SY
authors.lastname: Kim
authors.forename: Ji-Eun
authors.initials: JE
authors.lastname: Kim
authors.forename: Yoon Jun
authors.initials: YJ
authors.lastname: Kim
authors.forename: Kyou-Sup
authors.initials: KS
authors.lastname: Han
authors.forename: Hyun Kyung
authors.initials: HK
authors.lastname: Kim
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000925:Anticoagulants / Q000097:blood; D015415:Biomarkers / Q000097:blood; D001777:Blood Coagulation; D001780:Blood Coagulation Tests / Q000379:methods*; D001798:Blood Proteins / Q000032:analysis / Q000502:physiology; D065427:Factor Xa Inhibitors; D005260:Female; D006801:Humans; D008103:Liver Cirrhosis / Q000097:blood*; D008297:Male; D008875:Middle Aged; D011480:Protease Inhibitors / Q000494:pharmacology; D019851:Thrombophilia / Q000097:blood* / Q000175:diagnosis*; D055815:Young Adult
chemical_list: D000925:Anticoagulants; D015415:Biomarkers; D001798:Blood Proteins; D065427:Factor Xa Inhibitors; D011480:Protease Inhibitors; C026080:plasma protein Z
keywords: liver cirrhosis; protein Z; protein Z-dependent protease inhibitor; thrombin generation assay