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Published on: August 14, 2017
ADAMTS13, VWF, and Endotoxin Are Interrelated and Associated with the Severity of Liver Cirrhosis via
Hiroaki Takaya1, Tadashi Namisaki1, Shohei Asada1
1Department of Gastroenterology, 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.
Insights
The imbalance between ADAMTS13 activity and VWF antigen in liver cirrhosis is linked to endotoxin levels. Higher endotoxin correlates with altered ADAMTS13 and VWF:Ag, potentially driving hypercoagulability in cirrhosis.
Area of Science:
- Hematology
- Hepatology
- Biochemistry
Background:
- An imbalance between ADAMTS13 activity (ADAMTS13:AC) and VWF antigen (VWF:Ag) is linked to liver cirrhosis (LC) severity.
- The underlying cause of this imbalance in LC patients remains unclear.
Purpose of the Study:
- To investigate the relationship between ADAMTS13:AC, VWF:Ag, and endotoxin (Et) levels in patients with LC.
- To explore the association of these factors with LC severity and VWF multimer status.
Main Methods:
- Quantified ADAMTS13:AC and VWF:Ag using ELISA.
- Measured Et levels via chromogenic substrate assay.
- Assessed ADAMTS13 inhibitor (ADAMTS13:INH) and VWF multimer (VWFM) status.
Main Results:
- ADAMTS13:AC and VWF:Ag decreased with LC severity, while Et levels increased.
- High Et levels were associated with lower ADAMTS13:AC and higher VWF:Ag.
- Detectable ADAMTS13:INH and abnormal VWFM (normal or UL) correlated with higher Et levels.
Conclusions:
- ADAMTS13, VWF, and Et levels are interrelated and associated with LC severity.
- Endotoxin may play a crucial role in the ADAMTS13-VWF imbalance observed in liver cirrhosis.
- This interplay might contribute to the hypercoagulability state in patients with LC.
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