Fibrin clots from patients with acute-on-chronic liver failure are weaker than those from healthy individuals and patients with sepsis without underlying liver disease

Ellen G Driever; Iain Muntz; Vishal Patel; Jelle Adelmeijer; William Bernal; Gijsje H Koenderink; Ton Lisman

doi:10.1016/j.jtha.2023.06.011

Fibrin clots from patients with acute-on-chronic liver failure are weaker than those from healthy individuals and patients with sepsis without underlying liver disease

J Thromb Haemost. 2023 Oct;21(10):2747-2758. doi: 10.1016/j.jtha.2023.06.011. Epub 2023 Jun 17.

Authors

Ellen G Driever¹, Iain Muntz², Vishal Patel³, Jelle Adelmeijer¹, William Bernal³, Gijsje H Koenderink⁴, Ton Lisman⁵

Affiliations

¹ Surgical Research Laboratory, Department of Surgery, University Medical Center Groningen, University of Groningen, Groningen, the Netherlands.
² Department of Bionanoscience, Kavli Institute of Nanoscience, Delft University of Technology, Delft, the Netherlands.
³ Institute of Liver Studies, King's College Hospital NHS Foundation Trust, London, United Kingdom.
⁴ Department of Bionanoscience, Kavli Institute of Nanoscience, Delft University of Technology, Delft, the Netherlands. Electronic address: g.h.koenderink@tudelft.nl.
⁵ Surgical Research Laboratory, Department of Surgery, University Medical Center Groningen, University of Groningen, Groningen, the Netherlands. Electronic address: j.a.lisman@umcg.nl.

PMID: 37336436
DOI: 10.1016/j.jtha.2023.06.011

Abstract

Background: Previous studies identified decreased clot permeability, without differences in fibrin fiber density in clots, from patients with cirrhosis compared with those from healthy controls (HCs). Fibrinogen hypersialylation could be the reason for this discrepancy.

Objectives: The aim of this work was to study mechanical properties of clots and reassess clot permeability in relation to hypersialylation in patients with stable cirrhosis, acute decompensation, and acute-on-chronic liver failure (ACLF). Sepsis patients without liver disease were included to distinguish between liver-specific and inflammation-driven phenotypes.

Methods: Pooled plasma was used for rheology and permeability experiments. Permeability was assessed with compression using a rheometer and by liquid permeation. Purified fibrinogen treated with neuraminidase was used to study the effects of fibrinogen hypersialylation on liquid permeation.

Results: Mechanical properties of clots from patients with stable cirrhosis and acute decompensation were similar to those of clots from HCs, but clots from patients with ACLF were softer and ruptured at lower shear stress. Clots from sepsis patients without liver disease were stiffer than those from the other groups, but this effect disappeared after adjusting for increased plasma fibrinogen concentrations. Permeability was similar between clots under compression from HCs and clots under compression from patients but decreased with increasing disease severity in liquid permeation. Removal of fibrinogen sialic acid residues increased permeability more in patients than in controls.

Conclusion: Clots from patients with ACLF have weak mechanical properties despite unaltered fibrin fiber density. Previous liquid permeation experiments may have erroneously concluded that clots from patients with ACLF are prothrombotic as fibrinogen hypersialylation leads to underestimation of clot permeability in this setting, presumably due to enhanced water retention.

Keywords: fibrin; inflammation; liver cirrhosis; permeability; rheology; thrombosis.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Acute-On-Chronic Liver Failure*
Fibrin / chemistry
Fibrinogen / chemistry
Fibrinolysis
Fibrosis
Hemostatics*
Humans
Liver Cirrhosis / complications
Liver Cirrhosis / diagnosis
Sepsis* / complications
Thrombosis*

Substances

Fibrin
Fibrinogen
Hemostatics