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Increased platelet count and reticulated platelets in recently symptomatic versus asymptomatic carotid artery stenosis and in cerebral microembolic signal-negative patient subgroups: results from the HaEmostasis In carotid STenosis (HEIST) study

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Abstract

Background

The pathophysiological mechanisms responsible for the disparity in stroke risk between asymptomatic and symptomatic carotid stenosis patients are not fully understood. The functionally important reticulated platelet fraction and reticulocytes could play a role.

Objectives

We performed a prospective, multi-centre, observational analytical study comparing full blood count parameters and platelet production/turnover/activation markers in patients with asymptomatic versus recently symptomatic moderate (≥ 50–69%) or severe (≥ 70–99%) carotid stenosis.

Patients/methods

Data from 34 asymptomatic patients were compared with 43 symptomatic patients in the ‘early phase’ (≤ 4 weeks) and 37 of these patients in the ‘late phase’ (≥ 3 months) after TIA/ischaemic stroke. Reticulated platelets were quantified by whole blood flow cytometry and reticulated platelets and red cell reticulocytes by ‘automated assays’ (Sysmex XE-2100™). Bilateral simultaneous transcranial Doppler ultrasound monitoring classified patients as micro-embolic signal (MES)+ve or MES−ve.

Results

Mean platelet count was higher in early (216 × 109/L; P = 0.04) and late symptomatic (219 × 109/L; P = 0.044) than asymptomatic patients (194 × 109/L). Mean platelet volume was higher in early symptomatic than asymptomatic patients (10.8 vs. 10.45 fl; P = 0.045). Automated assays revealed higher % reticulated platelet fractions in early (5.78%; P < 0.001) and late symptomatic (5.11%; P = 0.01) than asymptomatic patients (3.48%). Red cell reticulocyte counts were lower in early (0.92%; P = 0.035) and late symptomatic (0.93%; P = 0.036) than asymptomatic patients (1.07%). The automated % reticulated platelet fraction was also higher in early symptomatic than asymptomatic MES−ve patients (5.7 vs. 3.55%; P = 0.001).

Discussion

The combination of increased platelet counts and a shift towards production of an increased population of larger, young, reticulated platelets could contribute to a higher risk of first or recurrent cerebrovascular events in recently symptomatic versus asymptomatic carotid stenosis, including those who are MES−ve.

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Acknowledgements

The remaining HEIST study group are: Tierney S FRCSI, Feely M FRCSI and Egan B FRCSI (Dept. of Vascular Surgery, AMNCH, Dublin, Ireland); Murphy SM FRCPI and Walsh RA FRCPI (Dept. of Neurology and Stroke Service, AMNCH, Dublin, and Academic Unit of Neurology, Trinity College Dublin, Ireland); Coughlan T FRCPI, Collins DR MD and O’Neill D MD (Dept. of Age-Related Healthcare and Stroke Service, AMNCH, Dublin, Ireland); Harbison JA MD (Dept. of Medicine for the Elderly/Stroke Service, St James’s Hospital, Dublin and Trinity College Dublin, Ireland), Madhavan P FRCS (Ed), O’Neill SM MCh and Colgan M-P MD (Dept. of Vascular Surgery, St James’s Hospital, Dublin, Ireland); Cox D PhD, Moran N PhD (Dept. of Molecular and Cellular Therapeutics, Royal College of Surgeons in Ireland, Dublin, Ireland), Hamilton G (University Dept. of Surgery, Royal Free Hampstead NHS Trust, London, UK). All HEIST collaborators qualified for authorship as they contributed to data acquisition or study design, and all critically appraised the manuscript for important intellectual content.

Dr Murphy’s research was funded by the Trinity College Dublin Innovation Bursary, the Meath Foundation, Ireland, Joint IICN/Merck Serono Fellowship in Neuroscience, The Vascular Neurology Research Foundation, Ireland, and by an unrestricted educational grant from Bayer HealthCare Ireland, and Verum Diagnostica, GmbH. Dr. Lim’s research was funded by the Meath Foundation, Ireland, The Irish Institute of Clinical Neuroscience (IICN)/Novartis Ireland Fellowship Grant, The Irish Heart Foundation Stroke Prevention Bursary, and by unrestricted educational grant funding from Biogen Idec Ireland. None of the above charities or funding bodies had any influence on design or conduct of this study, or had any influence on the decision to submit the final manuscript for publication. All authors critically reviewed and approved the final submitted manuscript. The manuscript has not been submitted elsewhere and has not been published elsewhere in whole or in part, except as an abstract.

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Authors and Affiliations

  1. Department of Neurology, The Adelaide and Meath Hospital, Dublin, incorporating the National Children’s Hospital (AMNCH), Dublin, Ireland

    S. J. X. Murphy, S. T. Lim & Dominick J. H. McCabe

  2. Vascular Neurology Research Foundation, The Adelaide and Meath Hospital, Dublin, incorporating the National Children’s Hospital (AMNCH), Tallaght, Dublin, Ireland

    Dominick J. H. McCabe

  3. Stroke Service, The Adelaide and Meath Hospital, Dublin, incorporating the National Children’s Hospital (AMNCH), Dublin, Ireland

    S. J. X. Murphy, S. T. Lim & Dominick J. H. McCabe

  4. Department of Haematology, The Adelaide and Meath Hospital, Dublin, incorporating the National Children’s Hospital (AMNCH), Dublin, Ireland

    D. Murphy & H. M. Enright

  5. Department of Neurology, St Vincent’s University Hospital, University College Dublin, Dublin, Ireland

    J. A. Kinsella

  6. Department of Clinical Neurosciences, Royal Free Campus, UCL Institute of Neurology, London, UK

    Dominick J. H. McCabe

  7. Irish Centre for Vascular Biology, Dublin, Ireland

    Dominick J. H. McCabe

  8. Academic Unit of Neurology, School of Medicine, Trinity College Dublin, Dublin, Ireland

    Dominick J. H. McCabe

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  1. S. J. X. Murphy
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For the HEIST study group

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Correspondence to Dominick J. H. McCabe.

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The authors declare that they have no competing interests.

Ethical standard

The study design and research protocol was approved by the Local Research Ethics Committee (Project/LREC Reference: 2011/31/02).

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Murphy, S.J.X., Lim, S.T., Kinsella, J.A. et al. Increased platelet count and reticulated platelets in recently symptomatic versus asymptomatic carotid artery stenosis and in cerebral microembolic signal-negative patient subgroups: results from the HaEmostasis In carotid STenosis (HEIST) study. J Neurol 265, 1037–1049 (2018). https://doi.org/10.1007/s00415-018-8797-8

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  • DOI: https://doi.org/10.1007/s00415-018-8797-8

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