ADAMTS13, VWF, and Endotoxin Are Interrelated and Associated with the Severity of Liver Cirrhosis via Hypercoagulability

Hiroaki Takaya; Tadashi Namisaki; Shohei Asada; Satoshi Iwai; Takahiro Kubo; Junya Suzuki; Masahide Enomoto; Yuki Tsuji; Yukihisa Fujinaga; Norihisa Nishimura; Yasuhiko Sawada; Kosuke Kaji; Hideto Kawaratani; Kei Moriya; Takemi Akahane; Masanori Matsumoto; Hitoshi Yoshiji

doi:10.3390/jcm11071835

ADAMTS13, VWF, and Endotoxin Are Interrelated and Associated with the Severity of Liver Cirrhosis via Hypercoagulability

J Clin Med. 2022 Mar 26;11(7):1835. doi: 10.3390/jcm11071835.

Authors

Hiroaki Takaya¹, Tadashi Namisaki¹, Shohei Asada¹, Satoshi Iwai¹, Takahiro Kubo¹, Junya Suzuki¹, Masahide Enomoto¹, Yuki Tsuji¹, Yukihisa Fujinaga¹, Norihisa Nishimura¹, Yasuhiko Sawada¹, Kosuke Kaji¹, Hideto Kawaratani¹, Kei Moriya¹, Takemi Akahane¹, Masanori Matsumoto², Hitoshi Yoshiji¹

Affiliations

¹ Department of Gastroenterology, Nara Medical University, Kashihara 634-8522, Japan.
² Department of Blood Transfusion Medicine, Nara Medical University, Kashihara 634-8522, Japan.

Abstract

ADAMTS13 specifically cleaves the multimeric von Willebrand factor (VWF), and an imbalance between ADAMTS13 activity (ADAMTS13:AC) and VWF antigen (VWF:Ag) levels is associated with the severity of liver cirrhosis (LC). However, the reason for this imbalance in patients with LC is unknown. This study investigated the relationship among ADAMTS13:AC, VWF:Ag, and endotoxin (Et) levels in patients with LC. ADAMTS13:AC and VWF:Ag levels were determined using ELISA, whereas Et levels were estimated using a chromogenic substrate assay. The levels of ADAMTS13 inhibitor (ADAMTS13:INH) were evaluated by measuring the extent that heat-inactivated patient's plasma reduces the ADAMTS13:AC of the control. The status (degraded, normal, or unusually large [UL]) of the VWF multimer (VWFM) was determined through vertical agarose gel electrophoresis. ADAMTS13:AC, VWF:Ag, and Et levels decreased, increased, and increased, respectively, with the severity of LC. Patients with cirrhosis with high Et levels had lower and higher ADAMTS13:AC and VWF:Ag levels, respectively, than those with low Et levels. Patients with cirrhosis with detectable ADAMTS13:INH had higher Et levels than those with undetectable ADAMTS13:INH. Patients whose VWFM was either normal or UL had higher Et levels than those with degraded VWFM. In conclusion, ADAMTS13, VWF, and Et may be interrelated and associated with the severity of LC via hypercoagulability.

Keywords: ADAMTS13; endotoxin; hypercoagulability; liver cirrhosis; von Willebrand factor.