title: Alterations in Fibrin Structure in Patients with Liver Diseases.
abstract: The hemostatic balance in patients with liver diseases is relatively well preserved due to concomitant alterations in pro- and antihemostatic pathways. Thrombin generation studies support the notion of hemostatic competence in liver diseases, but in such tests alterations in fibrinogen level and function are not taken into account. We have recently studied structural and functional properties of the fibrin clot in patients with liver diseases. Although we have confirmed previous findings that hypersialylation of the fibrinogen molecule in patients with liver diseases contributes to a defective fibrinogen-to-fibrin conversion, we have found that once the clot has been formed, it has a thrombogenic nature as assessed by permeability assays. These thrombogenic properties of the fibrin clot in cirrhosis relate to incompletely characterized intrinsic changes in the fibrinogen molecule, which may include oxidation and hypersialylation. In addition, in patients with nonalcoholic fatty liver disease thrombogenic properties of the fibrin clot are not only due to liver disease but also to obesity and the metabolic syndrome. During liver transplantation, the clot normalizes and becomes increasingly permeable, and the functional properties of the fibrin clot are markedly normalized by fibrinogen concentrate, when added to plasma samples in vitro. These new insights in the functional properties of the fibrin clot in patients with liver diseases facilitate a more rational approach to treatment and prevention of both bleeding and thrombotic complications.
authors.affiliation: Section of Hepatobiliary Surgery and Liver Transplantation, Department of Surgery, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.
authors.forename: Ton
authors.initials: T
authors.lastname: Lisman
authors.affiliation: Division of Cardiovascular and Diabetes Research, Thrombosis and Tissue Repair Group, Multidisciplinary Cardiovascular Research Centre and Leeds Institute for Cardiovascular and Metabolic Medicine, School of Medicine, University of Leeds, Leeds, United Kingdom.
authors.forename: Robert A S
authors.initials: RA
authors.lastname: Ariëns
mesh_terms: D005337:Fibrin / Q000378:metabolism*; D005340:Fibrinogen / Q000378:metabolism*; D006470:Hemorrhage / Q000097:blood / Q000209:etiology / Q000628:therapy; D006801:Humans; D008103:Liver Cirrhosis / Q000097:blood / Q000150:complications / Q000628:therapy; D011499:Protein Processing, Post-Translational; D013927:Thrombosis / Q000097:blood / Q000209:etiology / Q000628:therapy
chemical_list: D005337:Fibrin; D005340:Fibrinogen