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

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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.

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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

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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.

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Authors and Affiliations

  1. School of Medicine and Medical Sciences, University College Dublin, Dublin 4, Ireland

    Karl Egan, Barry Kevane & Fionnuala Ni Ainle

  2. SPHERE Research Group, Conway Institute, University College Dublin, Dublin 4, Ireland

    Karl Egan, Barry Kevane, Patricia Maguire & Fionnuala Ni Ainle

  3. Department of Hepatology, Mater Misericordiae University Hospital, Dublin 7, Ireland

    Audrey Dillon, Zita Galvin, Dermot Kenny & Stephen Stewart

  4. Molecular and Cellular Therapeutics, Royal College of Surgeons in Ireland, Dublin 2, Ireland

    Eimear Dunne

  5. Department of Haematology, Mater Misericordiae University Hospital, Dublin 7, Ireland

    Barry Kevane & Fionnuala Ni Ainle

Authors
  1. Karl Egan
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  2. Audrey Dillon
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  3. Eimear Dunne
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  4. Barry Kevane
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  9. Fionnuala Ni Ainle
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Correspondence to Fionnuala Ni Ainle.

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Egan, K., Dillon, A., Dunne, E. et al. Increased soluble GPVI levels in cirrhosis: evidence for early in vivo platelet activation. J Thromb Thrombolysis 43, 54–59 (2017). https://doi.org/10.1007/s11239-016-1401-0

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  • DOI: https://doi.org/10.1007/s11239-016-1401-0

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