title: Relationship between ADAMTS13 activity, von Willebrand factor antigen levels and platelet function in the early and late phases after TIA or ischaemic stroke.
abstract: BACKGROUND
  Reduced ADAMTS13 activity is seen in thrombotic thrombocytopenic purpura (TTP), and may lead to accumulation of prothrombotic ultra-large von Willebrand factor (ULVWF) multimers in vivo. ADAMTS13 activity and its relationship with VWF antigen (VWF:Ag) levels and platelet function in 'non-TTP related' TIA or ischaemic stroke has not been comprehensively studied.
  
  
  METHODS
  In this prospective pilot observational analytical case-control study, ADAMTS13 activity and VWF:Ag levels were quantified in platelet poor plasma in 53 patients in the early phase (≤ 4 weeks) and 34 of these patients in the late phase (≥ 3 months) after TIA or ischaemic stroke on aspirin. Data were compared with those from 22 controls not on aspirin. The impact of ADAMTS13 on platelet function in whole blood was quantified by measuring Collagen-ADP (C-ADP) and Collagen-Epinephrine closure times on a platelet function analyser (PFA-100(®)).
  
  
  RESULTS
  Median ADAMTS13 activity was significantly reduced in the early phase (71.96% vs. 95.5%, P <0.01) but not in the late phase after TIA or stroke compared with controls (86.3% vs. 95.5%, P=0.19). There was a significant inverse relationship between ADAMTS13 activity and VWF:Ag levels in the early phase (r=-0.31; P=0.024), but not in the late phase after TIA or stroke (P=0.74). There was a positive correlation between ADAMTS13 activity and C-ADP closure times in early phase patients only, likely mediated via VWF:Ag levels.
  
  
  CONCLUSIONS
  ADAMTS13 activity is reduced and VWF:Ag expression is increased within 4 weeks of TIA or ischaemic stroke onset, and can promote enhanced platelet adhesion and aggregation in response to stimulation with collagen and ADP via VWF-mediated pathways. These data improve our understanding of the dynamic haemostatic and thrombotic profiles of ischaemic cerebrovascular disease (CVD) patients, and are important in view of the potential future role that ADAMTS13 may have to play as an anti-thrombotic agent in CVD.
authors.affiliation: Department of Neurology, The Adelaide and Meath Hospital incorporating the National Children's Hospital, Trinity College, Dublin, Ireland; Stroke Service, The Adelaide and Meath Hospital, incorporating the National Children's Hospital, Trinity College, Dublin, Ireland; Stroke Research Group, UCL Institute of Neurology, The National Hospital for Neurology & Neurosurgery, UK; Department of Clinical Neurosciences, Royal Free Campus, UCL Institute of Neurology, The National Hospital for Neurology & Neurosurgery, UK; Haemostasis Research Unit, University College, London, UK. Electronic address: dominick.mccabe@amnch.ie.
authors.forename: Dominick J H
authors.initials: DJ
authors.lastname: McCabe
authors.affiliation: Department of Neurology, The Adelaide and Meath Hospital incorporating the National Children's Hospital, Trinity College, Dublin, Ireland; Stroke Service, The Adelaide and Meath Hospital, incorporating the National Children's Hospital, Trinity College, Dublin, Ireland.
authors.forename: Stephen J X
authors.initials: SJ
authors.lastname: Murphy
authors.affiliation: Haemostasis Research Unit, University College, London, UK.
authors.forename: Richard
authors.initials: R
authors.lastname: Starke
authors.affiliation: School of Immunity and Infection, University of Birmingham Medical School, UK.
authors.forename: Paul
authors.initials: P
authors.lastname: Harrison
authors.affiliation: Stroke Research Group, UCL Institute of Neurology, The National Hospital for Neurology & Neurosurgery, UK.
authors.forename: Martin M
authors.initials: MM
authors.lastname: Brown
authors.affiliation: Stroke Research Group, UCL Institute of Neurology, The National Hospital for Neurology & Neurosurgery, UK.
authors.forename: Paul S
authors.initials: PS
authors.lastname: Sidhu
authors.affiliation: Haemostasis Research Unit, University College, London, UK.
authors.forename: Ian J
authors.initials: IJ
authors.lastname: Mackie
authors.affiliation: Dept. of Haematology, University College, London, UK.
authors.forename: Marie
authors.initials: M
authors.lastname: Scully
authors.affiliation: Haemostasis Research Unit, University College, London, UK; Dept. of Haematology, University College, London, UK.
authors.forename: Samuel J
authors.initials: SJ
authors.lastname: Machin
mesh_terms: D051722:ADAM Proteins / Q000378:metabolism*; D000071120:ADAMTS13 Protein; D000368:Aged; D000369:Aged, 80 and over; D001792:Blood Platelets / Q000502:physiology*; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D002546:Ischemic Attack, Transient / Q000097:blood*; D008297:Male; D008875:Middle Aged; D010865:Pilot Projects; D010979:Platelet Function Tests; D020521:Stroke / Q000097:blood*; D013997:Time Factors; D014841:von Willebrand Factor / Q000378:metabolism*
chemical_list: D014841:von Willebrand Factor; D051722:ADAM Proteins; D000071120:ADAMTS13 Protein; C099604:ADAMTS13 protein, human
keywords: ADAMTS13; PFA-100(®); Platelets; Stroke; TIA; VWF antigen