Comprehensive analysis of ADAMTS13 in patients with liver cirrhosis

Masahito Uemura; Yoshihiro Fujimura; Masanori Matsumoto; Hiromichi Ishizashi; Seiji Kato; Tomomi Matsuyama; Ayami Isonishi; Masatoshi Ishikawa; Masato Yagita; Chie Morioka; Hitoshi Yoshiji; Tatsuhiro Tsujimoto; Norio Kurumatani; Hiroshi Fukui

doi:10.1160/TH08-01-0006

Thrombosis and Haemostasis, Table of Contents

Thromb Haemost 2008; 99(06): 1019-1029
DOI: 10.1160/TH08-01-0006

Blood Coagulation, Fibrinolysis and Cellular Haemostasis

Schattauer GmbH

Comprehensive analysis of ADAMTS13 in patients with liver cirrhosis

Masahito Uemura^*

¹Third Department of Internal Medicine

,

Yoshihiro Fujimura^*

²Department of Blood Transfusion Medicine

,

Masanori Matsumoto

²Department of Blood Transfusion Medicine

,

Hiromichi Ishizashi

²Department of Blood Transfusion Medicine

,

Seiji Kato

²Department of Blood Transfusion Medicine

,

Tomomi Matsuyama

¹Third Department of Internal Medicine

,

Ayami Isonishi

²Department of Blood Transfusion Medicine

,

Masatoshi Ishikawa

¹Third Department of Internal Medicine

,

Masato Yagita

⁴Kitano Hospital, Osaka, Japan

,

Chie Morioka

¹Third Department of Internal Medicine

,

Hitoshi Yoshiji

¹Third Department of Internal Medicine

,

Tatsuhiro Tsujimoto

¹Third Department of Internal Medicine

,

Norio Kurumatani

³Department of Community Health and Epidemiology, Nara Medical University, Kashihara, Nara, Japan

,

Hiroshi Fukui

¹Third Department of Internal Medicine

› Author Affiliations

Abstract

Summary

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.

Keywords

ADAMTSI3 activity - liver cirrhosis - von Willebrand factor - thrombocytopenia - inhibitor

Full Text

References

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