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

Détails

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Etat: Public
Version: Final published version
Licence: CC BY-NC-ND 4.0
ID Serval
serval:BIB_07141FDF59B0
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Institution
Titre
Biomarkers of liver dysfunction correlate with a prothrombotic and not with a prohaemorrhagic profile in patients with cirrhosis.
Périodique
JHEP reports
Auteur⸱e⸱s
Zermatten M.G., Fraga M., Calderara D.B., Aliotta A., Moradpour D., Alberio L.
ISSN
2589-5559 (Electronic)
ISSN-L
2589-5559
Statut éditorial
Publié
Date de publication
08/2020
Peer-reviewed
Oui
Volume
2
Numéro
4
Pages
100120
Langue
anglais
Notes
Publication types: Journal Article
Publication Status: epublish
Résumé
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.
Mots-clé
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
Web of science
Open Access
Oui
Création de la notice
11/08/2020 10:09
Dernière modification de la notice
21/11/2022 8:30
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