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Platelet-leucocyte aggregation is augmented in cirrhosis and further increased by platelet transfusion

Research output: Contribution to journalArticlepeer-review

S. Stoy, V. C. Patel, J. P. Sturgeon, G. K. Manakkat Vijay, T. Lisman, W. Bernal, D. L. Shawcross

Original languageEnglish
Pages (from-to)1375-1386
JournalAlimentary Pharmacology & Therapeutics
Volume47
Issue number10
Early online date12 Mar 2018
DOIs
Accepted/In press14 Feb 2018
E-pub ahead of print12 Mar 2018
Published31 May 2018

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  • Platelet-leucocyte aggregation is augmented_STOY_Firstonline12March2018_GREEN AAM

    Platelet_leucocyte_aggregation_is_augmented_STOY_Firstonline12March2018_GREEN_AAM.pdf, 908 KB, application/pdf

    Uploaded date:22 Mar 2018

    Version:Accepted author manuscript

    "This is the peer reviewed version of the following article: Støy S, Patel VC, Sturgeon JP, et al.Platelet-leucocyte aggregation is augmented in cirrhosis andfurther increased by platelet transfusion.Aliment PharmacolTher. 2018;00:1–12., which has been published in final form at https://doi.org/10.1111/apt.14600. This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Self-Archiving."

King's Authors

Abstract

BACKGROUND: Thrombocytopenia and circulating dysfunctional immune cells are commonly observed in patients with cirrhosis. Platelets may form complexes with neutrophils, monocytes and T cells modulating their function. We recently reported increased frequencies of platelet-complexed neutrophils in cirrhosis with evidence of neutrophil activation upon contact with healthy platelets in vitro. Whether this occurs in vivo following platelet transfusion and contributes to systemic inflammation and endothelial activation is unknown.

AIMS: To characterise platelet-leucocyte aggregation in cirrhosis and to determine whether elective platelet transfusion results in perturbations associated with changes in markers of haemostasis, inflammation or endothelial activation.

METHODS: We collected blood from cirrhotics (n = 19) before and following elective platelet transfusion. We measured platelet-leucocyte aggregation, activation and function, and markers of platelet activation, systemic inflammation and endothelial activation by flow cytometry. Haemostasis was assessed by thromboelastometry and plasma haemostatic proteins.

RESULTS: We observed a 2.5-fold increase in platelet-complexed neutrophils in patients with cirrhosis compared with healthy subjects and twofold more platelets attached per monocyte and T cell. All platelet-complexed leucocytes expressed higher levels of activation markers and platelet-complexed neutrophils had higher resting oxidative burst and phagocytic capacity than their nonplatelet-complexed counterparts (P < 0.001); most pronounced in patients with cirrhosis. Paradoxically, platelet-complexed leucocyte frequency decreased with increasing MELD score. Platelet transfusion increased soluble CD40 ligand (platelet activation marker), the frequency of platelet-complexed monocytes (P < 0.05) and improved haemostatic status.

CONCLUSION: Cirrhotic patients have activated circulating platelet-complexed leucocytes with increased platelet-monocyte aggregation following elective platelet transfusion. Elective platelet transfusion might therefore exacerbate immune dysfunction in cirrhosis.

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