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

E. Driever,I. Muntz,V. Patel,J. Adelmeijer,William Bernal,G. Koenderink,T. Lisman

Published 2023 in Journal of Thrombosis and Haemostasis

ABSTRACT

BACKGROUND AND AIM Previous studies identified decreased clot permeability without differences in fibrin fiber density in clots from patients with cirrhosis compared to healthy controls (HC). Fibrinogen hypersialylation could be the reason for this discrepancy. 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 (SC), acute decompensation (AD) and acute-on-chronic liver failure (ACLF). Non-liver sepsis (NLS) patients 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 SC and AD were similar to HC, but clots from ACLF patients were softer and ruptured at lower shear stress. Clots from NLS patients were stiffer than the other groups, but this effect disappeared after adjusting for increased plasma fibrinogen concentrations. Permeability was similar between HC and patient clots under compression, but decreased with increasing disease severity in liquid permeation. Removal of fibrinogen sialic acid residues increased permeability more in patients compared to controls. CONCLUSION Clots from ACLF patients have weak mechanical properties despite unaltered fibrin fiber density. Previous liquid permeation experiments may have erroneously concluded that clots from ACLF patients are prothrombotic as fibrinogen hypersialylation leads to underestimation of clot permeability in this setting, presumably due to enhanced water retention.

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