Comprehensive analysis of ADAMTS13 in patients with liver cirrhosis.
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.
Uemura
Masahito
M
Third Department of Internal Medicine, Nara Medical University, Kashihara, Nara, Japan. muemura@naramed-u.ac.jp
Fujimura
Yoshihiro
Y
Matsumoto
Masanori
M
Ishizashi
Hiromichi
H
Kato
Seiji
S
Matsuyama
Tomomi
T
Isonishi
Ayami
A
Ishikawa
Masatoshi
M
Yagita
Masato
M
Morioka
Chie
C
Yoshiji
Hitoshi
H
Tsujimoto
Tatsuhiro
T
Kurumatani
Norio
N
Fukui
Hiroshi
H
D051722:ADAM Proteins / Q000097:blood* / Q000172:deficiency / Q000276:immunology; D000071120:ADAMTS13 Protein; D000368:Aged; D001323:Autoantibodies / Q000097:blood; D015153:Blotting, Western; D016207:Cytokines / Q000097:blood; D015536:Down-Regulation; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D019694:Hepatitis B, Chronic / Q000150:complications / Q000201:enzymology; D019698:Hepatitis C, Chronic / Q000150:complications / Q000201:enzymology; D006801:Humans; D008103:Liver Cirrhosis / Q000150:complications / Q000201:enzymology* / Q000473:pathology / Q000821:virology; D008297:Male; D008875:Middle Aged; D010976:Platelet Count; D011697:Purpura, Thrombotic Thrombocytopenic / Q000201:enzymology / Q000209:etiology; D012720:Severity of Illness Index; D013927:Thrombosis / Q000201:enzymology / Q000209:etiology* / Q000473:pathology; D014841:von Willebrand Factor / Q000378:metabolism*
D001323:Autoantibodies; D016207:Cytokines; D014841:von Willebrand Factor; D051722:ADAM Proteins; D000071120:ADAMTS13 Protein; C099604:ADAMTS13 protein, human