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International Journal of Hematology
Published in: International Journal of Hematology 1/2010

01-01-2010 | Progress in Hematology

Pivotal role of ADAMTS13 function in liver diseases

Authors: Masahito Uemura, Yoshihiro Fujimura, Saiho Ko, Masanori Matsumoto, Yoshiyuki Nakajima, Hiroshi Fukui

Published in: International Journal of Hematology | Issue 1/2010

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Abstract

The liver is a major source of clotting and fibrinolytic proteins, and plays a central role in thrombo-regulation. Patients with advanced liver diseases tend to bleed because of reduced plasma levels of several clotting factors and thrombocytopenia, but they do also exhibit thrombotic complications. ADAMTS13 is a metalloproteinase, produced exclusively in hepatic stellate cells, and specifically cleaves highly multimeric von Willebrand factor (VWF). VWF plays a pivotal role in hemostasis and thrombosis, and its function is dependent on its multimeric state. Deficiency of ADAMTS13 results in accumulation of unusually large VWF multimers (UL-VWFM) in plasma, in turn induces platelet clumping or thrombi under high shear stress, followed by microcirculatory disturbances. Considering that UL-VWFM, the substrate of ADAMTS13, is produced in transformed vascular endothelial cells at sites of liver injury, decreased ADAMTS13 activity may be involved in not only sinusoidal microcirculatory disturbances, but also subsequent progression of liver injuries, eventually leading to multiorgan failure. This concept can be applied to the development or aggravation of liver diseases, including liver cirrhosis, alcoholic hepatitis, veno-occlusive disease, and adverse events after liver transplantation. These results promise to bring further understanding of the pathophysiology of liver diseases, and offer new insight for development of therapeutic strategies.
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Metadata
Title
Pivotal role of ADAMTS13 function in liver diseases
Authors
Masahito Uemura
Yoshihiro Fujimura
Saiho Ko
Masanori Matsumoto
Yoshiyuki Nakajima
Hiroshi Fukui
Publication date
01-01-2010
Publisher
Springer Japan
Published in
International Journal of Hematology / Issue 1/2010
Print ISSN: 0925-5710
Electronic ISSN: 1865-3774
DOI
https://doi.org/10.1007/s12185-009-0481-4

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