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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   *
1   Third Department of Internal Medicine
,
Yoshihiro Fujimura   *
2   Department of Blood Transfusion Medicine
,
Masanori Matsumoto
2   Department of Blood Transfusion Medicine
,
Hiromichi Ishizashi
2   Department of Blood Transfusion Medicine
,
Seiji Kato
2   Department of Blood Transfusion Medicine
,
Tomomi Matsuyama
1   Third Department of Internal Medicine
,
Ayami Isonishi
2   Department of Blood Transfusion Medicine
,
Masatoshi Ishikawa
1   Third Department of Internal Medicine
,
Masato Yagita
4   Kitano Hospital, Osaka, Japan
,
Chie Morioka
1   Third Department of Internal Medicine
,
Hitoshi Yoshiji
1   Third Department of Internal Medicine
,
Tatsuhiro Tsujimoto
1   Third Department of Internal Medicine
,
Norio Kurumatani
3   Department of Community Health and Epidemiology, Nara Medical University, Kashihara, Nara, Japan
,
Hiroshi Fukui
1   Third Department of Internal Medicine
› Author AffiliationsFinancial support: This work was supported in part by Grants-in-Aid for Scientific Research from the Japanese Ministry of Education, Culture, Sports, Science, and Technology (MU, YF) and from the Ministry of Health and Welfare of Japan for Blood Coagulation Abnormalities (YF).
Further Information

Publication History

Received 05 January 2008

Accepted after minor revision 13 April 2008

Publication Date:
27 November 2017 (online)

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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

* These authors contributed equally to this study.


 

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