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CC BY-NC-ND 4.0 · Thromb Haemost 2018; 118(08): 1397-1408
DOI: 10.1055/s-0038-1661393
Cellular Haemostasis and Platelets
Georg Thieme Verlag KG Stuttgart · New York

Major Changes of von Willebrand Factor Multimer Distribution in Cirrhotic Patients with Stable Disease or Acute Decompensation

Eszter Palyu   *
1   Division of Gastroenterology, Department of Internal Medicine, Faculty of Medicine, University of Debrecen, Debrecen, Hungary
,
Jolan Harsfalvi   *
2   Department of Biophysics and Radiation Biology, Semmelweis University, Budapest, Hungary
,
Tamas Tornai
1   Division of Gastroenterology, Department of Internal Medicine, Faculty of Medicine, University of Debrecen, Debrecen, Hungary
,
Maria Papp
1   Division of Gastroenterology, Department of Internal Medicine, Faculty of Medicine, University of Debrecen, Debrecen, Hungary
,
Miklos Udvardy
3   Department of Laboratory Medicine, Faculty of Medicine, University of Debrecen, Debrecen, Hungary
,
Katalin Szekeres-Csiki
3   Department of Laboratory Medicine, Faculty of Medicine, University of Debrecen, Debrecen, Hungary
,
Lajos Pataki
3   Department of Laboratory Medicine, Faculty of Medicine, University of Debrecen, Debrecen, Hungary
,
Karen Vanhoorelbeke
4   Laboratory for Thrombosis Research, IRF Life Science, KU Leuven Kulak, Kortrijk, Belgium
,
Hendrik B. Feys
5   Transfusion Research Center, Belgian Red Cross-Flanders, Ghent, Belgium
6   Faculty of Medicine and Health Sciences, Ghent University, Ghent, Belgium
,
Hans Deckmyn
4   Laboratory for Thrombosis Research, IRF Life Science, KU Leuven Kulak, Kortrijk, Belgium
,
Istvan Tornai
1   Division of Gastroenterology, Department of Internal Medicine, Faculty of Medicine, University of Debrecen, Debrecen, Hungary
› Author Affiliations Funding This work was supported by a research grant of the National Research Development and Innovation Office (NVKP-16-1-2016-0017).
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Publication History

21 March 2018

17 May 2018

Publication Date:
04 July 2018 (online)

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Abstract

Background There is an unstable balance between pro- and anti-haemostatic processes in patients with cirrhosis. We hypothesized, that in patients with acute decompensation (AD) the major alterations of von Willebrand factor (VWF) could contribute to the pro-thrombotic situation as compared to patients with stable (ST) cirrhosis.

Patients and Methods We analysed different parameters of VWF, including detailed multimer distribution by densitometry and platelet adhesion, together with a disintegrin-like and metalloproteinase with thrombospondin type-1 motifs 13 (ADAMTS13) activity and antigen and C-reactive protein (CRP) levels in patients with ST cirrhosis (n = 99), with AD (n = 54) and controls (n = 92).

Results VWF antigen, ristocetin co-factor as well as collagen-binding activities were elevated in both cirrhotic groups in a stepwise manner. There was a decrease in high and an increase in low molecular weight multimer ratios in the majority of ST cirrhosis. However, in 24 out of 54 AD patients, ultra-large VWF multimers (ultra-large molecular weight multimers [ULMWM]) were found. ADAMTS13 activity in ST and AD patients without ULMWM was similar to controls (median [interquartile range; IQR]%: 98 [67–132] and 91 [60–110] vs. 106 [88–117], respectively). The presence of ULMWM in AD patients was associated with low ADAMTS13 activity [33 (24–49)%] and high CRP level [23 (7.1–83.6) mg/L]. Adhesion of normal platelets showed a stepwise increase in the presence of cirrhotic plasmas, reaching the highest level in AD patients with ULMWM.

Conclusion Characteristic changes of VWF parameters are seen in ST cirrhosis. In AD patients, highly increased VWF and reduced ADAMTS13 activity could be found, along with the presence of ULMWM, which are possible markers and contributors of the disease progression.

Keywords

cirrhosis - acute decompensation - systemic inflammation - von Willebrand factor multimers - thrombotic micro-angiopathy

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