title: Increased platelet activation in early symptomatic vs. asymptomatic carotid stenosis and relationship with microembolic status: results from the Platelets and Carotid Stenosis Study.
abstract: BACKGROUND
  Cerebral microembolic signals (MES) may predict increased stroke risk in carotid stenosis. However, the relationship between platelet counts or platelet activation status and MES in symptomatic vs. asymptomatic carotid stenosis has not been comprehensively assessed.
  
  
  METHODS
  University teaching hospitals.
  
  
  METHODS
  This prospective, pilot observational study assessed platelet counts and platelet activation status, and the relationship between platelet activation and MES in asymptomatic vs. early (≤ 4 weeks after TIA/stroke) and late phase (≥ 3 months) symptomatic moderate or severe (≥ 50%) carotid stenosis patients. Full blood count measurements were performed, and whole blood flow cytometry was used to quantify platelet surface activation marker expression (CD62P and CD63) and circulating leucocyte-platelet complexes. Bilateral simultaneous transcranial Doppler ultrasound monitoring of the middle cerebral arteries was performed for 1 h to classify patients as MES positive or MES negative.
  
  
  RESULTS
  Data from 31 asymptomatic patients were compared with 46 symptomatic patients in the early phase, and 35 of these patients were followed up to the late phase after symptom onset. The median platelet count (211 vs. 200 × 10(9)  L(-1) ; P = 0.03) and the median percentage of lymphocyte-platelet complexes was higher in early symptomatic than asymptomatic patients (2.8 vs. 2.4%; P = 0.001). The percentage of lymphocyte-platelet complexes was higher in early symptomatic than in asymptomatic patients with ≥ 70% carotid stenosis (P = 0.0005) and symptomatic patients recruited within 7 days of symptom onset (P = 0.028). Complete TCD data were available in 25 asymptomatic, 31 early phase symptomatic and 27 late phase symptomatic patients. Twelve per cent of asymptomatic vs. 32% of early phase symptomatic (P = 0.02) and 19% of late phase symptomatic patients (P = 0.2) were MES positive. Early symptomatic MES-negative patients had a higher percentage of lymphocyte-platelet complexes than asymptomatic MES-negative patients (2.8 vs. 2.3%; P = 0.0085).
  
  
  CONCLUSIONS
  Recently, symptomatic carotid stenosis patients have had higher platelet counts (potentially reflecting increased platelet production, mobilization or reduced clearance) and platelet activation status than asymptomatic patients. MES were more frequently detected in early symptomatic than asymptomatic patients, but the differences between late symptomatic and asymptomatic groups were not significant. Increased lymphocyte-platelet complex formation in recently symptomatic vs. asymptomatic MES-negative patients indicates enhanced platelet activation in this early symptomatic subgroup. Platelet biomarkers, in combination with TCD, have the potential to aid risk-stratification in asymptomatic and symptomatic carotid stenosis patients.
authors.affiliation: Department of Neurology, The Adelaide and Meath Hospital Dublin/National Children's Hospital, Trinity College Dublin, Ireland.
authors.forename: J A
authors.initials: JA
authors.lastname: Kinsella
authors.forename: W O
authors.initials: WO
authors.lastname: Tobin
authors.forename: S
authors.initials: S
authors.lastname: Tierney
authors.forename: T M
authors.initials: TM
authors.lastname: Feeley
authors.forename: B
authors.initials: B
authors.lastname: Egan
authors.forename: D R
authors.initials: DR
authors.lastname: Collins
authors.forename: T
authors.initials: T
authors.lastname: Coughlan
authors.forename: D
authors.initials: D
authors.lastname: O'Neill
authors.forename: J
authors.initials: J
authors.lastname: Harbison
authors.forename: P
authors.initials: P
authors.lastname: Madhavan
authors.forename: D J
authors.initials: DJ
authors.lastname: Moore
authors.forename: S M
authors.initials: SM
authors.lastname: O'Neill
authors.forename: M P
authors.initials: MP
authors.lastname: Colgan
authors.forename: C P
authors.initials: CP
authors.lastname: Doherty
authors.forename: R P
authors.initials: RP
authors.lastname: Murphy
authors.forename: M
authors.initials: M
authors.lastname: Saqqur
authors.forename: N
authors.initials: N
authors.lastname: Moran
authors.forename: G
authors.initials: G
authors.lastname: Hamilton
authors.forename: D J H
authors.initials: DJ
authors.lastname: McCabe
mesh_terms: D000368:Aged; D058070:Asymptomatic Diseases; D015415:Biomarkers / Q000097:blood; D016893:Carotid Stenosis / Q000097:blood* / Q000150:complications / Q000276:immunology; D016009:Chi-Square Distribution; D005260:Female; D005434:Flow Cytometry; D006784:Hospitals, Teaching; D006801:Humans; D020766:Intracranial Embolism / Q000097:blood* / Q000000981:diagnostic imaging / Q000276:immunology; D002546:Ischemic Attack, Transient / Q000097:blood / Q000276:immunology; D016014:Linear Models; D008214:Lymphocytes / Q000276:immunology; D008297:Male; D008875:Middle Aged; D019007:P-Selectin / Q000097:blood; D010865:Pilot Projects; D015539:Platelet Activation; D010976:Platelet Count; D011237:Predictive Value of Tests; D011446:Prospective Studies; D012307:Risk Factors; D012720:Severity of Illness Index; D020521:Stroke / Q000097:blood / Q000209:etiology; D060149:Tetraspanin 30 / Q000097:blood; D013997:Time Factors; D018615:Ultrasonography, Doppler, Color; D017585:Ultrasonography, Doppler, Transcranial
chemical_list: D015415:Biomarkers; C554586:CD63 protein, human; D019007:P-Selectin; C546937:SELP protein, human; D060149:Tetraspanin 30
keywords: carotid stenosis; microembolic signals; platelet activation; transcranial doppler ultrasonography; whole blood flow cytometry