Thromb Haemost 2019; 119(05): 821-833
DOI: 10.1055/s-0039-1678666
Stroke, Systemic or Venous Thromboembolism
Georg Thieme Verlag KG Stuttgart · New York

Increased Leucocyte–Platelet Complex Formation in Recently Symptomatic versus Asymptomatic Carotid Stenosis Patients and in Micro-emboli Negative Subgroups

1  Department of Neurology, Adelaide and Meath Hospital, Dublin, incorporating the National Children's Hospital (AMNCH)/Tallaght University Hospital, Dublin, Ireland
2  Stroke Service, Adelaide and Meath Hospital, Dublin, incorporating the National Children's Hospital (AMNCH)/Tallaght University Hospital, Dublin, Ireland
,
Soon Tjin Lim
1  Department of Neurology, Adelaide and Meath Hospital, Dublin, incorporating the National Children's Hospital (AMNCH)/Tallaght University Hospital, Dublin, Ireland
2  Stroke Service, Adelaide and Meath Hospital, Dublin, incorporating the National Children's Hospital (AMNCH)/Tallaght University Hospital, Dublin, Ireland
,
Justin A. Kinsella
3  Department of Neurology, St Vincent’s University Hospital, University College Dublin, Dublin, Ireland
,
Sean Tierney
4  Department of Vascular Surgery, Adelaide and Meath Hospital, Dublin, incorporating the National Children’s Hospital (AMNCH)/Tallaght University Hospital, Dublin, Ireland
,
Bridget Egan
4  Department of Vascular Surgery, Adelaide and Meath Hospital, Dublin, incorporating the National Children’s Hospital (AMNCH)/Tallaght University Hospital, Dublin, Ireland
,
T. M. Feeley
4  Department of Vascular Surgery, Adelaide and Meath Hospital, Dublin, incorporating the National Children’s Hospital (AMNCH)/Tallaght University Hospital, Dublin, Ireland
5  Dublin Midlands Hospital Group, Ireland
,
Sinead M. Murphy
1  Department of Neurology, Adelaide and Meath Hospital, Dublin, incorporating the National Children's Hospital (AMNCH)/Tallaght University Hospital, Dublin, Ireland
6  Age-Related Health Care Department, Adelaide and Meath Hospital, Dublin, incorporating the National Children's Hospital (AMNCH)/Tallaght University Hospital, Dublin, Ireland
7  Academic Unit of Neurology, School of Medicine, Trinity College Dublin, Ireland
,
Richard A. Walsh
1  Department of Neurology, Adelaide and Meath Hospital, Dublin, incorporating the National Children's Hospital (AMNCH)/Tallaght University Hospital, Dublin, Ireland
7  Academic Unit of Neurology, School of Medicine, Trinity College Dublin, Ireland
,
D. R. Collins
2  Stroke Service, Adelaide and Meath Hospital, Dublin, incorporating the National Children's Hospital (AMNCH)/Tallaght University Hospital, Dublin, Ireland
6  Age-Related Health Care Department, Adelaide and Meath Hospital, Dublin, incorporating the National Children's Hospital (AMNCH)/Tallaght University Hospital, Dublin, Ireland
,
Tara Coughlan
2  Stroke Service, Adelaide and Meath Hospital, Dublin, incorporating the National Children's Hospital (AMNCH)/Tallaght University Hospital, Dublin, Ireland
6  Age-Related Health Care Department, Adelaide and Meath Hospital, Dublin, incorporating the National Children's Hospital (AMNCH)/Tallaght University Hospital, Dublin, Ireland
,
Desmond O'Neill
2  Stroke Service, Adelaide and Meath Hospital, Dublin, incorporating the National Children's Hospital (AMNCH)/Tallaght University Hospital, Dublin, Ireland
6  Age-Related Health Care Department, Adelaide and Meath Hospital, Dublin, incorporating the National Children's Hospital (AMNCH)/Tallaght University Hospital, Dublin, Ireland
,
Joseph A. Harbison
8  Department of Medicine for the Elderly/Stroke Service, St James Hospital/Trinity College Dublin, Ireland
,
Prakash Madhavan
9  Department of Vascular Surgery, St James Hospital/Trinity College Dublin, Dublin, Ireland
,
Sean M. O'Neill
9  Department of Vascular Surgery, St James Hospital/Trinity College Dublin, Dublin, Ireland
,
Mary P. Colgan
9  Department of Vascular Surgery, St James Hospital/Trinity College Dublin, Dublin, Ireland
,
Dermot Cox
10  Department of Molecular and Cellular Therapeutics, Royal College of Surgeons in Ireland, Dublin, Ireland
,
Niamh Moran
10  Department of Molecular and Cellular Therapeutics, Royal College of Surgeons in Ireland, Dublin, Ireland
,
George Hamilton
11  Department of Vascular Surgery, University Department of Surgery, Royal Free Hampstead NHS Trust, London, United Kingdom
,
Dominick J. H. McCabe
1  Department of Neurology, Adelaide and Meath Hospital, Dublin, incorporating the National Children's Hospital (AMNCH)/Tallaght University Hospital, Dublin, Ireland
2  Stroke Service, Adelaide and Meath Hospital, Dublin, incorporating the National Children's Hospital (AMNCH)/Tallaght University Hospital, Dublin, Ireland
6  Age-Related Health Care Department, Adelaide and Meath Hospital, Dublin, incorporating the National Children's Hospital (AMNCH)/Tallaght University Hospital, Dublin, Ireland
12  Vascular Neurology Research Foundation, c/o Department of Neurology, Adelaide and Meath Hospital, Dublin, incorporating the National Children's Hospital (AMNCH)/Tallaght University Hospital, Dublin, Ireland
13  Department of Clinical Neurosciences, Royal Free Campus, UCL Institute of Neurology, London, United Kingdom
14  Irish Centre for Vascular Biology, Dublin, Ireland
› Author Affiliations
Funding 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 unrestricted educational grants 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 an 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.
Further Information

Publication History

10 October 2018

04 January 2019

Publication Date:
15 February 2019 (eFirst)

Abstract

Introduction Cerebral micro-embolic signals (MES) predict risk of stroke in carotid stenosis patients. However, MES-negative ‘recently symptomatic patients’ also have a higher stroke risk than ‘asymptomatic patients’. Differences in platelet activation status may contribute to this disparity in risk.

Methods This prospective, observational study assessed platelet biomarkers and their relationship with MES in asymptomatic versus symptomatic moderate (≥50–69%) or severe (≥70–99%) carotid stenosis patients. Full blood count parameters were measured and whole-blood flow cytometry was used to quantify platelet surface CD62P and CD63 expression and leucocyte–platelet complex formation. Bilateral simultaneous transcranial Doppler ultrasound of the middle cerebral arteries classified patients as ‘MES positive’ or ‘MES negative’.

Results Data from 34 asymptomatic patients were compared with those from 43 symptomatic patients in the ‘early phase’ (≤ 4 weeks) and 37 of these symptomatic patients in the ‘late phase’ (≥ 3 months) after transient ischaemic attack/ischaemic stroke. There were no differences in %CD62P or %CD63 expression between early or late symptomatic and asymptomatic patients overall (p > 0.05). The percentage of lymphocyte–platelet complexes was higher in early symptomatic than in asymptomatic patients (2.8 vs. 2.16%; p < 0.001). MES were more commonly observed in early symptomatic (31.4%; p = 0.027) but not in late symptomatic (6.7%; p = 0.996) versus asymptomatic patients (7.1%). The percentage of lymphocyte–platelet complexes was higher in early symptomatic than in asymptomatic MES-negative patients (2.7 vs. 2.17%; p = 0.02).

Conclusion These data add to the evidence that leucocyte–platelet complex formation/platelet activation is increased in recently symptomatic versus asymptomatic patients, and may contribute to the pathogenesis of first and subsequent strokes in carotid stenosis patients, including those who are MES negative.

Note

All HEIST collaborators qualified for authorship because they contributed to data acquisition or study design, and all critically appraised and approved the final submitted manuscript for important intellectual content.