Clinical and pathophysiological perspectives on haemostasis, inflammation, and thrombo-haemorrhagic risk in cirrhosis.

Authors

Alberto Zanetto, Kymentie Ferdinande, Marco Senzolo

Published in

EXCLI journal. Volume 25. Pages 1346-1375. Epub Aug 17, 2026.

Abstract

Haemostasis in cirrhosis is a dynamic process characterised by a fragile equilibrium. Haemostatic alterations become more pronounced during acute decompensation and acute-on-chronic liver failure, conditions driven by increasing systemic inflammation. When compounded by bacterial infection or acute kidney injury, additional alterations may emerge, predisposing to bleeding and thrombosis. Recent data indicate an interplay between haemostasis and inflammation in chronic liver disease, with implications for disease progression and thrombo-haemorrhagic complications. In this review, we discuss evolving knowledge across four interconnected domains. First, we summarise novel insights into the haemostatic status in cirrhosis derived from functional assays assessing platelet aggregation, total thrombus formation, thrombin and plasmin generation. Second, we examine the interplay between haemostasis and inflammation, focusing on immunohaemostasis, immunothrombosis, and coagulation-driven fibrogenesis as contributors to disease progression, with altered gut-liver axis signalling as an important upstream trigger. Third, we review evolving concepts in portal vein thrombosis and venous thromboembolism, highlighting accumulating evidence that portal vein thrombosis may represent a vascular remodelling disorder characterised by endothelial-to-mesenchymal transition, driven by portal hypertension-induced low shear stress, inflammation, infection, and gut-derived inflammatory stimuli, establishing a microenvironment permissive to secondary thrombus formation. Finally, we discuss procedure-related bleeding risk assessment, underscoring the need for a multidimensional framework integrating procedure- and patient-related factors, clinical trajectory, systemic inflammation, and functional haemostatic testing. These advances reinforce an integrated paradigm in which haemostasis, inflammation, and liver disease progression are highly interconnected. Improved understanding of this interface may enhance risk stratification and identify novel therapeutic targets in advanced chronic liver disease. See also the graphical abstract(Fig. 1).

PMID:
42840238
Bibliographic data and abstract were imported from PubMed on 07 Oct 2026.

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