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World J Hepatol. Jul 8, 2015; 7(13): 1772-1781
Published online Jul 8, 2015. doi: 10.4254/wjh.v7.i13.1772
Relevance of ADAMTS13 to liver transplantation and surgery
Saiho Ko, Hisanao Chisuwa, Masanori Matsumoto, Yoshihiro Fujimura, Eiji Okano, Yoshiyuki Nakajima
Saiho Ko, Department of Surgery, Nara Prefecture General Medical Center, Nara 631-0846, Japan
Saiho Ko, Eiji Okano, Yoshiyuki Nakajima, Departement of Surgery, Nara Medical University, Kashihara, Nara 634-8522, Japan
Hisanao Chisuwa, Department of Surgery, Kofu City Hospital, Kofu, Yamanashi 400-0832, Japan
Masanori Matsumoto, Yoshihiro Fujimura, Departement of Blood Transfusion Medicine, Nara Medical University, Kashihara, Nara 634-8522, Japan
Author contributions: Nakajima Y conducted entire study; Fujimura Y constructed study design of the analysis of ADAMTS13 and von Willebrand factor related molecules; Matsumoto M instructed the analysis of ADAMTS13 and von Willebrand factor related molecules and refined and improved the entire study; Chisuwa H performed analysis and management of pediatric liver transplant patients; Ko S and Okano E conceived the idea of the study and performed analysis of data, adult liver transplantion, syrgery, and management of the patients.
Conflict-of-interest statement: The authors declare no conflict of interest associated with this study.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Correspondence to: Saiho Ko, Director, Departement of Surgery, Nara Prefecture General Medical Center, 1-30-1 Hiramatsu, Nara-city, Nara 631-0846, Japan. saihoko@naramed-u.ac.jp
Telephone: +81-742-466001 Fax: +81-742-466011
Received: August 24, 2014
Peer-review started: August 24, 2014
First decision: September 16, 2014
Revised: March 23, 2015
Accepted: April 10, 2015
Article in press: April 14, 2015
Published online: July 8, 2015
Processing time: 320 Days and 3.7 Hours
Abstract

A disintegrin-like and metalloproteinase with thrombospondin type-1 motifs 13 (ADAMTS13) specifically cleaves unusually-large von Willebrand factor (VWF) multimers under high shear stress, and down-regulates VWF function to form platelet thrombi. Deficiency of plasma ADAMTS13 activity induces a life-threatening systemic disease, termed thrombotic microangiopathy (TMA) including thrombotic thrombocytopenic purpura (TTP). Children with advanced biliary cirrhosis due to congenital biliary atresia sometimes showed pathological features of TMA, with a concomitant decrease of plasma ADAMTS13 activity. Disappearance of their clinical findings of TTP after successful liver transplantation suggested that the liver is a major organ producing plasma ADAMTS13. In situ hybridization analysis showed that ADAMTS13 was produced by hepatic stellate cells. Subsequently, it was found that ADADTS13 was not merely responsible to development of TMA and TTP, but also related to some kinds of liver dysfunction after liver transplantation. Ischemia-reperfusion injury and acute rejection in liver transplant recipients were often associated with marked decrease of ADAMTS13 and concomitant formation of unusually large VWF multimers without findings of TMA/TTP. The similar phenomenon was observed also in patients who underwent hepatectomy for liver tumors. Imbalance between ADAMTS13 and VWF in the hepatic sinusoid might cause liver damage due to microcirculatory disturbance. It can be called as “local TTP like mechanism” which plays a crucial role in liver dysfunction after liver transplantation and surgery.

Keywords: A disintegrin-like and metalloproteinase with thrombospondin type-1 motifs 13; Thrombocytopenia; Microcirculation; Liver dysfunction; von Willebrand factor; Liver transplantation; Acute rejection; Ischemia-reperfusion injury; Hepatectomy; Liver surgery; Local thrombotic thrombocytopenic purpura like mechanism

Core tip: A disintegrin-like and metalloproteinase with thrombospondin type-1 motifs 13 (ADAMTS13) is a cleaving protease of von Willebrand factor (VWF). The deficiency of this molecule is known to cause thrombotic thrombocytopenic purpura (TTP). Recent studies revealed that ADAMTS13 might have functional relevance to pathogenesis of various liver disease separately from the development of TTP. Imbalance between ADAMTS13 and VWF in the hepatic sinusoid might cause liver damage due to microcirculatory disturbance. It can be called as “local TTP like mechanism” which plays a crucial role in liver dysfunction after liver transplantation and surgery including ischemia reperfusion injury and acute rejection.