title: Increased thrombin generation potential in symptomatic versus asymptomatic moderate or severe carotid stenosis and relationship with cerebral microemboli.
abstract: BACKGROUND
  The importance of thrombin generation in the pathogenesis of TIA or stroke and its relationship with cerebral microembolic signals (MES) in asymptomatic and symptomatic carotid stenosis has not been comprehensively assessed.
  
  
  METHODS
  Plasma thrombin generation parameters from patients with moderate or severe (≥ 50%) asymptomatic carotid stenosis were compared with those from patients with symptomatic carotid stenosis in the early (≤ 4 weeks) and late phases (≥ 3 months) after TIA or stroke in this prospective, pilot observational study. Thrombin generation profile was longitudinally assessed in symptomatic patients with data at each time point. Bilateral transcranial Doppler ultrasound monitoring of the middle cerebral arteries was performed whenever possible to classify patients as MES-positive or MES-negative.
  
  
  RESULTS
  Data from 31 asymptomatic, 46 'early symptomatic' and 35 'late symptomatic' patients were analysed. Peak thrombin (344.2 nM vs 305.3 nM; p = 0.01) and endogenous thrombin potential (1772.4 vs 1589.7; p = 0.047) were higher in early symptomatic than asymptomatic patients. Peak thrombin production decreased in symptomatic patients followed up from the early to late phase after TIA or stroke (339.7 nM vs 308.6 nM; p = 0.02). Transcranial Doppler ultrasound data were available in 25 asymptomatic, 31 early symptomatic and 27 late symptomatic patients. Early symptomatic MES-positive patients had a shorter 'time-to-peak thrombin' than asymptomatic MES-positive patients (p=0.04), suggesting a more procoagulant state in this early symptomatic subgroup.
  
  
  CONCLUSIONS
  Thrombin generation potential is greater in patients with recently symptomatic than asymptomatic carotid stenosis, and decreases over time following TIA or stroke associated with carotid stenosis. These data improve our understanding of the haemostatic/thrombotic biomarker profile in moderate-severe carotid stenosis.
authors.affiliation: Department of Neurology, The Adelaide and Meath Hospital, Dublin, incorporating the National Children's Hospital, Trinity College Dublin, Dublin, Ireland.
authors.forename: J A
authors.initials: JA
authors.lastname: Kinsella
authors.affiliation: Department of Neurology, The Adelaide and Meath Hospital, Dublin, incorporating the National Children's Hospital, Trinity College Dublin, Dublin, Ireland.
authors.forename: W O
authors.initials: WO
authors.lastname: Tobin
authors.affiliation: Department of Neurology, The Adelaide and Meath Hospital, Dublin, incorporating the National Children's Hospital, Trinity College Dublin, Dublin, Ireland.
authors.forename: G F
authors.initials: GF
authors.lastname: Kavanagh
authors.affiliation: Haemostasis Research Group, St James Hospital, Trinity College Dublin, Dublin, Ireland.
authors.forename: J S
authors.initials: JS
authors.lastname: O'Donnell
authors.affiliation: Haemostasis Research Group, St James Hospital, Trinity College Dublin, Dublin, Ireland.
authors.forename: R T
authors.initials: RT
authors.lastname: McGrath
authors.affiliation: Department of Vascular Surgery, The Adelaide and Meath Hospital, Dublin, incorporating the National Children's Hospital, Trinity College Dublin, Dublin, Ireland.
authors.forename: S
authors.initials: S
authors.lastname: Tierney
authors.affiliation: Department of Vascular Surgery, The Adelaide and Meath Hospital, Dublin, incorporating the National Children's Hospital, Trinity College Dublin, Dublin, Ireland.
authors.forename: T M
authors.initials: TM
authors.lastname: Feeley
authors.affiliation: Department of Vascular Surgery, The Adelaide and Meath Hospital, Dublin, incorporating the National Children's Hospital, Trinity College Dublin, Dublin, Ireland.
authors.forename: B
authors.initials: B
authors.lastname: Egan
authors.affiliation: Age-Related Health Care, The Adelaide and Meath Hospital, Dublin, incorporating the National Children's Hospital, Trinity College Dublin, Dublin, Ireland Stroke Service, The Adelaide and Meath Hospital, Dublin, incorporating the National Children's Hospital, Trinity College Dublin, Dublin, Ireland.
authors.forename: D
authors.initials: D
authors.lastname: O'Neill
authors.affiliation: Age-Related Health Care, The Adelaide and Meath Hospital, Dublin, incorporating the National Children's Hospital, Trinity College Dublin, Dublin, Ireland Stroke Service, The Adelaide and Meath Hospital, Dublin, incorporating the National Children's Hospital, Trinity College Dublin, Dublin, Ireland.
authors.forename: D R
authors.initials: DR
authors.lastname: Collins
authors.affiliation: Age-Related Health Care, The Adelaide and Meath Hospital, Dublin, incorporating the National Children's Hospital, Trinity College Dublin, Dublin, Ireland Stroke Service, The Adelaide and Meath Hospital, Dublin, incorporating the National Children's Hospital, Trinity College Dublin, Dublin, Ireland.
authors.forename: T
authors.initials: T
authors.lastname: Coughlan
authors.affiliation: Departments of Medicine for the Elderly/Stroke Service, St James Hospital, Trinity College Dublin, Dublin, Ireland.
authors.forename: J A
authors.initials: JA
authors.lastname: Harbison
authors.affiliation: Department of Neurology, St James Hospital, Trinity College Dublin, Dublin, Ireland.
authors.forename: C P
authors.initials: CP
authors.lastname: Doherty
authors.affiliation: Department of Vascular Surgery, St James Hospital, Trinity College Dublin, Dublin, Ireland.
authors.forename: P
authors.initials: P
authors.lastname: Madhavan
authors.affiliation: Department of Vascular Surgery, St James Hospital, Trinity College Dublin, Dublin, Ireland.
authors.forename: D J
authors.initials: DJ
authors.lastname: Moore
authors.affiliation: Department of Vascular Surgery, St James Hospital, Trinity College Dublin, Dublin, Ireland.
authors.forename: S M
authors.initials: SM
authors.lastname: O'Neill
authors.affiliation: Department of Vascular Surgery, St James Hospital, Trinity College Dublin, Dublin, Ireland.
authors.forename: M P
authors.initials: MP
authors.lastname: Colgan
authors.affiliation: Department of Medicine (Neurology), University of Calgary, Alberta, Canada.
authors.forename: M
authors.initials: M
authors.lastname: Saqqur
authors.affiliation: Department of Neurology, The Adelaide and Meath Hospital, Dublin, incorporating the National Children's Hospital, Trinity College Dublin, Dublin, Ireland Stroke Service, The Adelaide and Meath Hospital, Dublin, incorporating the National Children's Hospital, Trinity College Dublin, Dublin, Ireland.
authors.forename: R P
authors.initials: RP
authors.lastname: Murphy
authors.affiliation: Department of Molecular and Cellular Therapeutics, Royal College of Surgeons in Ireland, Dublin, Ireland.
authors.forename: N
authors.initials: N
authors.lastname: Moran
authors.affiliation: University Department of Surgery, Royal Free Hampstead NHS Trust, London, UK.
authors.forename: G
authors.initials: G
authors.lastname: Hamilton
authors.affiliation: Department of Neurology, The Adelaide and Meath Hospital, Dublin, incorporating the National Children's Hospital, Trinity College Dublin, Dublin, Ireland Stroke Service, The Adelaide and Meath Hospital, Dublin, incorporating the National Children's Hospital, Trinity College Dublin, Dublin, Ireland Department of Clinical Neurosciences, Royal Free Campus, UCL Institute of Neurology, London, UK.
authors.forename: D J H
authors.initials: DJ
authors.lastname: McCabe
mesh_terms: D000368:Aged; D016893:Carotid Stenosis / Q000188:drug therapy / Q000378:metabolism*; D005260:Female; D006801:Humans; D020766:Intracranial Embolism / Q000000981:diagnostic imaging / Q000188:drug therapy / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D010975:Platelet Aggregation Inhibitors / Q000627:therapeutic use; D012307:Risk Factors; D013917:Thrombin / Q000096:biosynthesis*; D017585:Ultrasonography, Doppler, Transcranial
chemical_list: D010975:Platelet Aggregation Inhibitors; D013917:Thrombin
keywords: CEREBROVASCULAR DISEASE; STROKE