An unbalance between von Willebrand factor and ADAMTS13 in acute liver failure: Implications for hemostasis and clinical outcome

Emerging evidence supports the concept of a rebalanced hemostatic state in liver disease as a result of a commensurate decline in prohemostatic and antihemostatic drivers. In the present study, we assessed levels and functionality of the platelet‐adhesive protein von Willebrand factor (VWF) and its...

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Published in:Hepatology (Baltimore, Md.) Vol. 58; no. 2; pp. 752 - 761
Main Authors: Hugenholtz, Greg C. G., Adelmeijer, Jelle, Meijers, Joost C. M., Porte, Robert J., Stravitz, R. Todd, Lisman, Ton
Format: Journal Article
Language:English
Published: United States Wolters Kluwer Health, Inc 01.08.2013
Subjects:
Acute Lung Injury - blood
Acute Lung Injury - diagnosis
Acute Lung Injury - physiopathology
ADAM Proteins - blood
ADAMTS13 Protein
Adult
Biomarkers - blood
Case-Control Studies
Collagen - metabolism
Female
Hemostasis - physiology
Hepatology
Humans
Liver
Liver Failure, Acute - blood
Liver Failure, Acute - diagnosis
Liver Failure, Acute - physiopathology
Male
Middle Aged
Molecular weight
Plasma
Platelet Adhesiveness - physiology
Prognosis
Risk Factors
Thrombosis - epidemiology
Thrombosis - physiopathology
von Willebrand Factor - metabolism
ISSN:0270-9139, 1527-3350, 1527-3350
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Summary:Emerging evidence supports the concept of a rebalanced hemostatic state in liver disease as a result of a commensurate decline in prohemostatic and antihemostatic drivers. In the present study, we assessed levels and functionality of the platelet‐adhesive protein von Willebrand factor (VWF) and its cleaving protease ADAMTS13 in the plasma of patients with acute liver injury and acute liver failure (ALI/ALF). Furthermore, we explored possible associations between VWF, ADAMTS13, and disease outcome. We analyzed the plasma of 50 patients taken on the day of admission for ALI/ALF. The plasma of 40 healthy volunteers served as controls. VWF antigen levels were highly elevated in patients with ALI/ALF. In contrast, the collagen‐binding activity and the ratio of the VWF ristocetin cofactor activity and VWF antigen was significantly decreased when compared with healthy controls. Also, the proportion of high molecular weight VWF multimers was reduced, despite severely decreased ADAMTS13 levels. In spite of these functional defects, platelet adhesion and aggregation were better supported by plasma of patients with ALI/ALF when compared with control plasma. Low ADAMTS13 activity, but not high VWF antigen, was associated with poor outcome in patients with ALI/ALF as evidenced by higher grades of encephalopathy, higher transplantation rates, and lower survival. VWF or ADAMTS13 levels were not associated with bleeding or thrombotic complications. Conclusion: Highly elevated levels of VWF in plasma of patients with ALI/ALF support platelet adhesion, despite a relative loss of function of the molecule. Furthermore, low ADAMTS13 activity is associated with progressive liver failure in the patient cohort, which might be attributed to platelet‐induced microthrombus formation in the diseased liver resulting from a substantially unbalanced VWF/ADAMTS13 ratio. (Hepatology 2013;58:752–761)
Bibliography:These authors contributed equally to this work.
This study was supported in part by a grant from the Stichting Tekke Huizinga Fonds.
This work was an ancillary study of the Acute Liver Failure Study Group (National Institute of Diabetes and Digestive and Kidney Diseases (grant U01 DK58369; William M. Lee, M.D., Principal Investigator).
Potential conflict of interest: Nothing to report.
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ISSN:0270-9139
1527-3350
1527-3350
DOI:10.1002/hep.26372