PB1058 - Mechanical properties of fibrin clots from patients with acute-on-chronic liver failure are inferior to those of healthy individuals and patients with sepsis without underlying liver disease

Tuesday, June 27, 2023

18:30 – 19:30 ET

Room: Exhibition

Presenting Author(s)

ED

Ellen Driever

PhD Student
Surgical Research Laboratory, Department of Surgery, Univeristy Medical Center Groningen, Groningen, the Netherlands
Groningen, Groningen, Netherlands

Co-Author(s)

IM

Iain Muntz

Post-doc
Department of Bionanoscience, Kavli Institute of Nanoscience, Delft University of Technology, Delft, The Netherlands
Delft, Zuid-Holland, Netherlands
VP

Vishal Patel

MD PhD
Institute of Liver Studies, King’s College Hospital NHS Foundation Trust, London, United Kingdom
London, England, United Kingdom
JA

Jelle Adelmeijer

Analyst
UMCG
Groningen, Groningen, Netherlands
WB

William Bernal

Professor
Institute of Liver Studies, King’s College Hospital NHS Foundation Trust, London, United Kingdom
London, England, United Kingdom
GK

Gijsje H. Koenderink

Professor
Department of Bionanoscience, Kavli Institute of Nanoscience, Delft University of Technology, Delft, the Netherlands
Delft, Zuid-Holland, Netherlands
Ton Lisman, PhD

Professor of Experimental Surgery
UMCG
Groningen, Groningen, Netherlands

Background: Previous studies identified a paradoxically decreased permeability without differences in fibrin fiber density in cirrhosis patients compared with healthy controls (HC). Increased fibrinogen sialic acid content could be the reason for this discrepancy.

Aims: The aim of this study was to investigate the mechanical properties of clots from patients with stable cirrhosis (SC), acute decompensation (AD) and acute-on-chronic liver failure (ACLF).

Methods: Pooled plasma from HC, SC, AD, ACLF and non-liver sepsis (NLS) patients was used for rheology and permeability experiments. Permeability was measured under the force of compression using a rheometer and by liquid permeation. Purified fibrinogen treated with neuraminidase was used to study the effects of fibrinogen sialic acid content on liquid permeation.

Results: Mechanical properties of clots from patients with SC and AD are similar to clots from HC, but clots from ACLF patients are softer and rupture at lower shear stress. Clots from NLS patients have stiffer properties than the other groups, but this effects disappears after correction for high plasma fibrinogen concentrations in these patients. Permeability is similar between HC and patients under the force of compression, but decreases with increasing disease severity in liquid permeation. Clot permeability increases after removal of fibrinogen sialic acid residues.

Conclusion(s): We found that clots from ACLF patients have weak mechanical properties. High fibrinogen concentrations compensate for weak clot properties in NLS patients. Previous liquid permeation experiments may have falsely concluded that clots from cirrhotic patients are prothrombotic due to effects of increased fibrinogen sialic acid content.