Biomarkers of liver dysfunction correlate with a prothrombotic and not with a prohaemorrhagic profile in patients with cirrhosis.

Details

Serval ID
serval:BIB_07141FDF59B0
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Biomarkers of liver dysfunction correlate with a prothrombotic and not with a prohaemorrhagic profile in patients with cirrhosis.
Journal
JHEP reports
Author(s)
Zermatten M.G., Fraga M., Calderara D.B., Aliotta A., Moradpour D., Alberio L.
ISSN
2589-5559 (Electronic)
ISSN-L
2589-5559
Publication state
Published
Issued date
08/2020
Peer-reviewed
Oui
Volume
2
Number
4
Pages
100120
Language
english
Notes
Publication types: Journal Article
Publication Status: epublish
Abstract
Different liver dysfunction biomarkers are used to assess the bleeding risk of patients with cirrhosis, either as such or included in bleeding risk assessment scores. Since the current model of coagulation in patients with cirrhosis describes a procoagulant tendency with increasing severity according to Child-Pugh stage, we decided to investigate the relation between liver dysfunction biomarkers and thrombin generation. Our aim was to verify their adequacy for bleeding risk assessment.
We performed a prospective single-centre study including 260 patients with liver cirrhosis. Thrombin generation was measured using ST Genesia® Thrombin Generation System without and with thrombomodulin in order to assess the role of proteins C and S. Relations between thrombin generation and Child-Pugh/model for end-stage liver disease (MELD) scores, prothrombin time (PT)/international normalised ratio (INR), activated partial thromboplastin time (aPTT), factor V activity, albumin, and total bilirubin were assessed.
Thrombomodulin-mediated inhibition of thrombin generation was significantly decreased in patients with liver cirrhosis compared with healthy donors (p <0.0001) and in Child-Pugh B and C compared with A (p <0.0001 [A-B], 0.4515 [B-C], <0.0001 [A-C]). Thrombomodulin-mediated inhibition significantly decreased with increasing PT/INR, aPTT, and total bilirubin levels and with decreasing factor V activity and albumin levels.
Worsening liver dysfunction biomarkers reflect an increasing prothrombotic profile in patients with liver cirrhosis. In particular, prolonged PT/INR and aPTT as well as decreasing factor V activity are related to an increasing thrombotic risk and not to an increasing bleeding risk. These parameters should not be used to assess bleeding risk due to haemostatic anomalies in patients with liver cirrhosis. Alternative biomarkers for bleeding risk assessment in patients with liver cirrhosis need to be developed.
We demonstrate that the laboratory parameters used to assess bleeding risk of patients with liver disease, e.g. prothrombin time/international normalised ratio (PT/INR) and activated partial thromboplastin time (aPTT), are inadequate for this purpose because they are correlated with a prothrombotic coagulation profile. In this article, we highlight the need for alternative parameters to assess bleeding risk in patients with liver disease.
Keywords
Bilirubin, Blood coagulation tests, Coagulation, ETP, endogenous thrombin potential, INR, international normalised ratio, Liver cirrhosis, MELD, model for end-stage liver disease, NASH, non-alcoholic steatohepatitis, PFP, platelet-free plasma, PT, prothrombin time, Serum albumin, TM, thrombomodulin, Thrombosis, VTE, venous thromboembolism, aPTT, activated partial thromboplastin time
Pubmed
Open Access
Yes
Create date
11/08/2020 11:09
Last modification date
19/11/2020 7:26
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