title: The platelet inhibiting effect of a clopidogrel bolus dose in patients on long-term acetylsalicylic acid treatment.
abstract: BACKGROUND
  Addition of clopidogrel to patients treated with ASA has been shown to decrease the incidence of in-stent thrombosis after percutaneous coronary interventions. However, it has also been reported that up to 30% of patients do not achieve adequate platelet inhibition from standard dosages of ASA and clopidogrel. There is a demand for reliable methods to measure the individual platelet inhibiting effect of this combination therapy.
  
  
  METHODS
  The primary aim of the present investigation was to compare three methods for evaluation of the platelet inhibiting effect of a clopidogrel bolus dose in patients on long-term acetylsalicylic acid treatment. Thirty patients presenting for coronary angiography/PCI were included. Two patients were excluded due to technical problems. All patients were on 75-100 mg ASA/day for at least 8 days. Blood samples were analysed before and 16 h after a 300 mg clopidogrel bolus dose. The platelet inhibiting effect was measured with (1) Whole blood flow cytometry (17 patients); (2) a bed-side test, Platelet Mapping assay for the thrombelastograph (28 patients); and (3) PFA (Platelet function analyser) -100 (26 patients).
  
  
  RESULTS
  With flow cytometry, the percentage of platelets expressing P-selectin (p=0.03) on their surface decreased significantly after the bolus dose of clopidogrel. There was also a reduction of platelets binding fibrinogen when stimulated with ADP. A significantly (p=0.002) increased platelet inhibition could also be demonstrated with Platelet Mapping. PFA-100 could not measure any significant platelet inhibiting effect of clopidogrel.
  
  
  CONCLUSIONS
  A significant platelet inhibition could be demonstrated with flow cytometry and the Platelet Mapping assay, but not with PFA-100. However, levels of response for the individual patient with these three methods were inconsistent. Further studies are needed to evaluate how the results correlate to the clinical risk of thrombosis and bleeding.
authors.affiliation: Department of Cardiac and Thoracic Anaesthesia and Surgery, Akademiska University Hospital, 751 85 Uppsala, Sweden. ulrica.alstrom@akademiska.se
authors.forename: Ulrica
authors.initials: U
authors.lastname: Alström
authors.forename: Hans
authors.initials: H
authors.lastname: Tydén
authors.forename: Jonas
authors.initials: J
authors.lastname: Oldgren
authors.forename: Agneta
authors.initials: A
authors.lastname: Siegbahn
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Ståhle
mesh_terms: D000368:Aged; D001241:Aspirin / Q000627:therapeutic use*; D001780:Blood Coagulation Tests / Q000295:instrumentation / Q000379:methods / Q000592:standards; D000077144:Clopidogrel; D004305:Dose-Response Relationship, Drug; D004359:Drug Therapy, Combination; D005260:Female; D005340:Fibrinogen / Q000378:metabolism; D005434:Flow Cytometry; D006801:Humans; D008297:Male; D008875:Middle Aged; D019007:P-Selectin / Q000032:analysis; D010975:Platelet Aggregation Inhibitors / Q000097:blood / Q000627:therapeutic use*; D011485:Protein Binding / Q000187:drug effects; D012016:Reference Values; D013916:Thrombelastography / Q000379:methods; D013988:Ticlopidine / Q000031:analogs & derivatives* / Q000097:blood / Q000627:therapeutic use; D013997:Time Factors
chemical_list: D019007:P-Selectin; D010975:Platelet Aggregation Inhibitors; D005340:Fibrinogen; D000077144:Clopidogrel; D013988:Ticlopidine; D001241:Aspirin