title: Comparison of a new P2Y12 receptor specific platelet aggregation test with other laboratory methods in stroke patients on clopidogrel monotherapy.
abstract: BACKGROUND
  Clinical studies suggest that 10-50% of patients are resistant to clopidogrel therapy. ADP induced platelet aggregation, a widely used test to monitor clopidogrel therapy, is affected by aspirin and is not specific for the P2Y12 receptor inhibited by clopidogrel.
  
  
  OBJECTIVE
  To develop a P2Y12-specific platelet aggregation test and to compare it with other methods used for monitoring clopidogrel therapy.
  
  
  METHODS
  Study population included 111 patients with the history of ischemic stroke being on clopidogrel monotherapy and 140 controls. The effect of clopidogrel was tested by a newly developed ADP(PGE1) aggregation test in which prostaglandin E1 treated platelets are used. Results of conventional ADP induced platelet aggregation, VerifyNow P2Y12 assay and ADP(PGE1) aggregation were compared to those obtained by flow cytometric analysis of vasodilator stimulated phosphoprotein (VASP) phosphorylation. Reference intervals for all assays were determined according to the guidelines of Clinical Laboratory Standards Institute.
  
  
  RESULTS
  The P2Y12-specificity of ADP(PGE1) test was proven by comparing it with ADP aggregation in the presence of P2Y1 antagonist, adenosine 3', 5'-diphosphate. The method was not influenced by aspirin treatment. Approximately 50% of patients were clopidogrel resistant by conventional ADP aggregation and VerifyNow tests. The ADP(PGE1) method and the VASP phosphorylation assay identified 25.9% and 11.7% of patients as non-responders, respectively. ADP(PGE1) aggregation showed good correlation with VASP phosphorylation and had high diagnostic efficiency.
  
  
  CONCLUSIONS
  The new ADP(PGE1) method is a reliable test for monitoring P2Y12 receptor inhibition by platelet aggregation. As a subset of patients are non-responders, monitoring clopidogrel therapy by adequate methods is essential.
authors.affiliation: Clinical Research Center, University of Debrecen, Medical and Health Science Center, Debrecen, Hungary.
authors.forename: Zsuzsa
authors.initials: Z
authors.lastname: Bagoly
authors.forename: Ferenc
authors.initials: F
authors.lastname: Sarkady
authors.forename: Tünde
authors.initials: T
authors.lastname: Magyar
authors.forename: János
authors.initials: J
authors.lastname: Kappelmayer
authors.forename: Endre
authors.initials: E
authors.lastname: Pongrácz
authors.forename: László
authors.initials: L
authors.lastname: Csiba
authors.forename: László
authors.initials: L
authors.lastname: Muszbek
mesh_terms: D000244:Adenosine Diphosphate / Q000494:pharmacology; D000328:Adult; D000368:Aged; D000527:Alprostadil / Q000494:pharmacology; D001792:Blood Platelets / Q000187:drug effects / Q000378:metabolism; D015815:Cell Adhesion Molecules / Q000378:metabolism; D019411:Clinical Laboratory Techniques / Q000379:methods; D000077144:Clopidogrel; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D008297:Male; D008840:Microfilament Proteins / Q000378:metabolism; D008875:Middle Aged; D010750:Phosphoproteins / Q000378:metabolism; D010766:Phosphorylation / Q000187:drug effects; D010974:Platelet Aggregation / Q000187:drug effects*; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology; D010979:Platelet Function Tests / Q000379:methods; D058921:Purinergic P2Y Receptor Antagonists / Q000627:therapeutic use; D058925:Receptors, Purinergic P2Y12 / Q000378:metabolism*; D015203:Reproducibility of Results; D020521:Stroke / Q000097:blood / Q000188:drug therapy*; D013988:Ticlopidine / Q000031:analogs & derivatives* / Q000627:therapeutic use; D000098662:Vasodilator-Stimulated Phosphoprotein
chemical_list: D015815:Cell Adhesion Molecules; D008840:Microfilament Proteins; D010750:Phosphoproteins; D010975:Platelet Aggregation Inhibitors; D058921:Purinergic P2Y Receptor Antagonists; D058925:Receptors, Purinergic P2Y12; D000098662:Vasodilator-Stimulated Phosphoprotein; D000244:Adenosine Diphosphate; D000077144:Clopidogrel; C010840:adenosine 3'-phosphate-5'-phosphate; D000527:Alprostadil; D013988:Ticlopidine