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Journal of Thrombosis and Thrombolysis

, Volume 43, Issue 1, pp 54–59 | Cite as

Increased soluble GPVI levels in cirrhosis: evidence for early in vivo platelet activation

  • Karl Egan
  • Audrey Dillon
  • Eimear Dunne
  • Barry Kevane
  • Zita Galvin
  • Patricia Maguire
  • Dermot Kenny
  • Stephen Stewart
  • Fionnuala Ni Ainle
Article

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/106 platelets/ml vs. cirrhosis; 0.048 ± 0.04 ng/106 platelets/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.

Keywords

Cirrhosis Collagen Glycoprotein VI Platelet activation Shedding 

Abbreviations

BMI

Body mass index

GPVI

Glycoprotein VI

sGPVI

Soluble glycoprotein VI

LMWH

Low molecular weight heparin

LSM

Liver stiffness measurement

MELD

Model for end-stage liver disease

ALD

Alcoholic liver disease

HCV

Hepatitis C virus

NAFLD

Non alcoholic fatty liver disease

AIH

Autoimmune hepatitis

HH

Hereditary haemochromatosis

PBC

Primary biliary cholangitis

PAR1

Protease activated receptor 1

HSC

Hepatitic stellate cells

Notes

Acknowledgments

This work was supported by the ‘Friends of the Rotunda’, the Health Research Board of Ireland (Health Research Award R13728), and by Science Foundation Ireland under Grant No 10/CE/B1821.

Author’s contributions

KE, SS, and FNA designed the study. AD, ED, BK, and ZG collected the samples. KE, ED, and BK performed the experiments. KE, AD, and ED analysed the data. KE, AD, PM, DK, SS, and FNA prepared and edited the manuscript.

Compliance with ethical standards

Conflict of Interest

The authors declare no conflict of interest.

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Copyright information

© Springer Science+Business Media New York 2016

Authors and Affiliations

  • Karl Egan
    • 1
    • 2
  • Audrey Dillon
    • 3
  • Eimear Dunne
    • 4
  • Barry Kevane
    • 1
    • 2
    • 5
  • Zita Galvin
    • 3
  • Patricia Maguire
    • 2
  • Dermot Kenny
    • 3
  • Stephen Stewart
    • 3
  • Fionnuala Ni Ainle
    • 1
    • 2
    • 5
  1. 1.School of Medicine and Medical SciencesUniversity College DublinDublin 4Ireland
  2. 2.SPHERE Research Group, Conway InstituteUniversity College DublinDublin 4Ireland
  3. 3.Department of HepatologyMater Misericordiae University HospitalDublin 7Ireland
  4. 4.Molecular and Cellular TherapeuticsRoyal College of Surgeons in IrelandDublin 2Ireland
  5. 5.Department of HaematologyMater Misericordiae University HospitalDublin 7Ireland

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