Comprehensive analysis of ADAMTS13 in patients with liver cirrhosis

• Published in: Thrombosis and haemostasis Vol. 99; no. 6; p. 1019
• Main Authors: Uemura, Masahito, Fujimura, Yoshihiro, Matsumoto, Masanori, Ishizashi, Hiromichi, Kato, Seiji, Matsuyama, Tomomi, Isonishi, Ayami, Ishikawa, Masatoshi, Yagita, Masato, Morioka, Chie, Yoshiji, Hitoshi, Tsujimoto, Tatsuhiro, Kurumatani, Norio, Fukui, Hiroshi
• Format: Journal Article
• Language: English
• Published: Germany 01.06.2008
• Subjects: ADAM Proteins - blood; ADAM Proteins - deficiency; ADAM Proteins - immunology; ADAMTS13 Protein; Aged; Autoantibodies - blood; Blotting, Western; Cytokines - blood; Down-Regulation; Enzyme-Linked Immunosorbent Assay; Female; Hepatitis B, Chronic - complications; Hepatitis B, Chronic - enzymology; Hepatitis C, Chronic - complications; Hepatitis C, Chronic - enzymology; Humans; Liver Cirrhosis - complications; Liver Cirrhosis - enzymology; Liver Cirrhosis - pathology; Liver Cirrhosis - virology; Male; Middle Aged; Platelet Count; Purpura, Thrombotic Thrombocytopenic - enzymology; Purpura, Thrombotic Thrombocytopenic - etiology; Severity of Illness Index; Thrombosis - enzymology; Thrombosis - etiology; Thrombosis - pathology; von Willebrand Factor - metabolism
• ISSN: 0340-6245
• DOI: 10.1160/TH08-01-0006

Decreased plasma ADAMTS13 activity (ADAMTS13:AC) results in the accumulation of unusually large von Willebrand factor multimer (UL-VWFM) and the formation of platelet thrombi. It remains controversial whether or not plasma ADAMTS13:AC decreases in patients with liver cirrhosis (LC), and its relationship to clinical features has not been fully investigated. We measured ADAMTS13:AC and its related parameters in plasma in 33 patients with chronic hepatitis (CH) and in 109 patients with LC. ADAMTS13:AC decreased with increasing severity of liver disease (controls means 100%, CH 87%, Child A-LC 79%, Child B-LC 63%, and Child C-LC 31%), and showed severe deficiency (<3% of controls) in five end-stage LC. Activities measured by act-ELISA strongly correlated with those determined by the VWFM assay and ADAMTS13 antigen. Multivariate analysis showed Child-Pugh score and spleen volume independent factors contributing to ADAMTS13:AC. VWFM patterns were normal in 53% of cases, degraded in 31%, and unusually large in 16%. Patients with unusually large VWFM had the lowest ADAMTS13:AC as well as the highest Child-Pugh score, serum creatinine and blood ammonia levels. Plasma inhibitor against ADAMTS13 detected in 83% of patients with severe to moderate ADAMTS13:AC deficiency mostly showed marginal zone between 0.5 and 1.0 BU/ml. The IgG-type autoantibodies specific to plasma derived-ADAMTS13 was detected by Western blot in only five end-stage LC with severe ADAMTS13:AC deficiency. In conclusion, both plasma ADAMTS13 activity and antigen levels decreased with increasing severity of cirrhosis. An imbalance between the decreased ADAMTS13:AC and its increased substrate may reflect the predisposing state for platelet thrombi formation in patients with advanced LC.