title: Platelet function under aspirin, clopidogrel, and both after ischemic stroke: a case-crossover study.
abstract: OBJECTIVE
  Combined antiplatelet agents may offer additive protection over single drugs after stroke. We investigated whether platelet activation is reduced under combined aspirin and clopidogrel compared with each drug alone.
  
  
  METHODS
  In a case-crossover study, 31 patients with previous atherothrombotic or lacunar stroke who were treated with aspirin (100 to 300 mg/d) received clopidogrel (75 mg/d) and both aspirin and clopidogrel for 4 weeks. Platelet function in whole blood was studied after each treatment period and in healthy control subjects to assess activation-dependent antigens CD62p and CD63 by flow cytometry and collagen/epinephrine (CEPI-CT) and collagen/ADP (CADP-CT) closure times with the platelet function analyzer PFA-100, which investigates platelet-related function under shear stress.
  
  
  RESULTS
  CD62p expression and CD63 expression were not different under the 3 treatment regimens. CD63 but not CD62p expression was lower in control subjects than in stroke patients regardless of the antiplatelet treatment (P<0.05). CEPI-CT was prolonged under aspirin and aspirin plus clopidogrel compared with clopidogrel monotherapy (P<0.0001). CADP-CT was longer under combination therapy than under aspirin (P=0.0009) or clopidogrel (P=0.0074) or in control subjects (P=0.0010), mainly because of strong prolongation in a patient subgroup (28%).
  
  
  CONCLUSIONS
  CD63 expression reflecting the release of platelet lysosomes is consistently increased after stroke and incompletely suppressed by treatment with aspirin, clopidogrel, or both. The strong prolongation of CADP-CT under combined aspirin and clopidogrel in a patient subgroup may indicate a lower risk of thrombosis but also a higher risk of hemorrhage. The predictive value of platelet activation parameters requires investigation in prospective studies.
authors.affiliation: Neurology Department, University of Heidelberg, Germany. graua@klilu.de
authors.forename: Armin J
authors.initials: AJ
authors.lastname: Grau
authors.forename: Sven
authors.initials: S
authors.lastname: Reiners
authors.forename: Christoph
authors.initials: C
authors.lastname: Lichy
authors.forename: Florian
authors.initials: F
authors.lastname: Buggle
authors.forename: Andreas
authors.initials: A
authors.lastname: Ruf
mesh_terms: D015703:Antigens, CD / Q000378:metabolism; D001241:Aspirin / Q000627:therapeutic use*; D001792:Blood Platelets / Q000187:drug effects / Q000378:metabolism / Q000502:physiology; D002545:Brain Ischemia / Q000097:blood / Q000188:drug therapy* / Q000378:metabolism; D016022:Case-Control Studies; D000077144:Clopidogrel; D018592:Cross-Over Studies; D004359:Drug Therapy, Combination; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D008297:Male; D008875:Middle Aged; D019007:P-Selectin / Q000378:metabolism; D015539:Platelet Activation / Q000187:drug effects; D010975:Platelet Aggregation Inhibitors / Q000627:therapeutic use*; D010980:Platelet Membrane Glycoproteins / Q000378:metabolism; D055502:Secondary Prevention; D020521:Stroke / Q000097:blood / Q000188:drug therapy* / Q000378:metabolism; D060149:Tetraspanin 30; D013988:Ticlopidine / Q000031:analogs & derivatives / Q000627:therapeutic use*
chemical_list: D015703:Antigens, CD; C554586:CD63 protein, human; D019007:P-Selectin; D010975:Platelet Aggregation Inhibitors; D010980:Platelet Membrane Glycoproteins; D060149:Tetraspanin 30; D000077144:Clopidogrel; D013988:Ticlopidine; D001241:Aspirin