title: Increased soluble GPVI levels in cirrhosis: evidence for early in vivo platelet activation.
abstract: Cirrhosis is a consequence of prolonged liver injury and is characterised by extensive tissue fibrosis: the deposition of collagen-rich extracellular matrix. The haemostatic balance is disordered in cirrhosis and coagulation activation appears to promote fibrosis. In spite of recent studies demonstrating a role for anticoagulant therapy in preventing cirrhosis progression, there has not been a change in clinical practice, suggesting that physicians are reluctant to anticoagulate patients with cirrhosis due to bleeding risks. Platelets play an important role in facilitating coagulation. Glycoprotein VI (GPVI) is a platelet-specific collagen receptor that is shed from the platelet surface in a metalloproteinase-dependent manner in response to GPVI ligation and coagulation activation. Our aim was to use soluble GPVI levels to determine whether there was evidence for collagen and coagulation-induced platelet activation in early, well-compensated cirrhosis. Plasma soluble GPVI levels were quantified in 46 patients with mixed aetiology cirrhosis and 55 healthy controls using an immunoassay. In the cirrhosis group, soluble GPVI levels were significantly increased (5.8 ± 4.4 ng/ml, n = 46) compared to healthy controls (3.3 ± 3.4 ng/ml, n = 55, p < 0.05). This increase in soluble GPVI levels was still evident when levels were adjusted for platelet count (Healthy controls; 0.015 ± 0.018 ng/106platelets/ml vs. cirrhosis; 0.048 ± 0.04 ng/106platelets/ml, p < 0.0001). This study provides evidence for early platelet activation in patients with well-compensated cirrhosis. This may have translational implications for prognosis, treatment, and risk stratification.
authors.affiliation: School of Medicine and Medical Sciences, University College Dublin, Dublin 4, Ireland.|SPHERE Research Group, Conway Institute, University College Dublin, Dublin 4, Ireland.
authors.forename: Karl
authors.initials: K
authors.lastname: Egan
authors.affiliation: Department of Hepatology, Mater Misericordiae University Hospital, Dublin 7, Ireland.
authors.forename: Audrey
authors.initials: A
authors.lastname: Dillon
authors.affiliation: Molecular and Cellular Therapeutics, Royal College of Surgeons in Ireland, Dublin 2, Ireland.
authors.forename: Eimear
authors.initials: E
authors.lastname: Dunne
authors.affiliation: School of Medicine and Medical Sciences, University College Dublin, Dublin 4, Ireland.|SPHERE Research Group, Conway Institute, University College Dublin, Dublin 4, Ireland.|Department of Haematology, Mater Misericordiae University Hospital, Dublin 7, Ireland.
authors.forename: Barry
authors.initials: B
authors.lastname: Kevane
authors.affiliation: Department of Hepatology, Mater Misericordiae University Hospital, Dublin 7, Ireland.
authors.forename: Zita
authors.initials: Z
authors.lastname: Galvin
authors.affiliation: SPHERE Research Group, Conway Institute, University College Dublin, Dublin 4, Ireland.
authors.forename: Patricia
authors.initials: P
authors.lastname: Maguire
authors.affiliation: Department of Hepatology, Mater Misericordiae University Hospital, Dublin 7, Ireland.
authors.forename: Dermot
authors.initials: D
authors.lastname: Kenny
authors.affiliation: Department of Hepatology, Mater Misericordiae University Hospital, Dublin 7, Ireland.
authors.forename: Stephen
authors.initials: S
authors.lastname: Stewart
authors.affiliation: School of Medicine and Medical Sciences, University College Dublin, Dublin 4, Ireland. fniainle@mater.ie.|SPHERE Research Group, Conway Institute, University College Dublin, Dublin 4, Ireland. fniainle@mater.ie.|Department of Haematology, Mater Misericordiae University Hospital, Dublin 7, Ireland. fniainle@mater.ie.
authors.forename: Fionnuala Ni
authors.initials: FN
authors.lastname: Ainle
mesh_terms: D000368:Aged; D016022:Case-Control Studies; D005260:Female; D006801:Humans; D008103:Liver Cirrhosis / Q000097:blood*; D008297:Male; D008875:Middle Aged; D015539:Platelet Activation; D010976:Platelet Count; D010980:Platelet Membrane Glycoproteins / Q000032:analysis* / Q000502:physiology; D012995:Solubility
chemical_list: D010980:Platelet Membrane Glycoproteins; C098341:platelet membrane glycoprotein VI
keywords: Cirrhosis; Collagen; Glycoprotein VI; Platelet activation; Shedding