title: Thrombin and plasmin generation in patients with liver disease.
abstract: Patients with liver disease frequently have multiple hemostatic abnormalities. Coagulation and fibrinolytic factors and inhibitors may decrease as the result of impaired synthesis and/or enhanced catabolism. In order to assess the actual degree of activation of coagulation and fibrinolytic systems in liver disease, plasma levels of thrombin-antithrombin III complex (TAT) and plasmin-alpha 2-antiplasmin complex (PAP) were measured together with cross-linked fibrin derivatives (XDP), tissue-type plasminogen activator (t-PA), and plasminogen activator inhibitor (PAI-1) in 31 patients with liver disease (five patients with acute hepatitis, seven with chronic hepatitis, nine with liver cirrhosis, and ten with hepatocellular carcinoma). Mean plasma levels of TAT (mean 4.2 +/- SD 4.0 micrograms/L), PAP (0.7 +/- 0.7 mg/L), and XDP (374 +/- 518 micrograms/L) were significantly elevated in patients with liver disease as compared with normal subjects (TAT of 1.7 +/- 0.3 micrograms/L, PAP of 0.2 +/- 0.1 mg/L, and XDP of 30 +/- 14 micrograms/L; P less than 0.005). Plasma concentrations of t-PA and PAI-1 antigens were also elevated. When plotted by the disease categories, the magnitude of elevations of these parameters was variable among subgroups. Patients with acute hepatitis had considerably higher TAT levels. The mean PAP values were relatively high in chronic hepatitis and hepatocellular carcinoma, in which an elevation of the t-PA/PAI-1 ratio was observed. Although clearance of TAT and PAP should be evaluated in the future, these findings suggest that excessive amounts of thrombin and plasmin are actually generated in patients with liver disease.
authors.affiliation: First Department of Internal Medicine, Niigata University School of Medicine, Japan.
authors.forename: H
authors.initials: H
authors.lastname: Takahashi
authors.forename: W
authors.initials: W
authors.lastname: Tatewaki
authors.forename: K
authors.initials: K
authors.lastname: Wada
authors.forename: A
authors.initials: A
authors.lastname: Yoshikawa
authors.forename: A
authors.initials: A
authors.lastname: Shibata
mesh_terms: D000990:Antithrombin III / Q000032:analysis; D001780:Blood Coagulation Tests; D005341:Fibrinolysin / Q000032:analysis / Q000096:biosynthesis*; D006801:Humans; D008107:Liver Diseases / Q000097:blood*; D013917:Thrombin / Q000032:analysis / Q000096:biosynthesis*; D000979:alpha-2-Antiplasmin / Q000032:analysis
chemical_list: D000979:alpha-2-Antiplasmin; D000990:Antithrombin III; D013917:Thrombin; D005341:Fibrinolysin