title: Platelet count, not oxidative stress, may contribute to inadequate platelet inhibition by aspirin.
abstract: BACKGROUND
  Several patient characteristics have been shown to increase the risk of inadequate platelet inhibition by aspirin, yet underlying mechanisms remain mostly unknown. We explored whether oxidative stress, via isoprostane formation, was associated with inadequate platelet response to aspirin. Additionally, we sought to investigate whether individual pre-selected demographic, hematological or biochemical parameters further increased the risk of inadequate platelet response to aspirin.
  
  
  METHODS
  Two hundred consecutive subjects suffering from stable coronary artery disease and under daily aspirin therapy were enrolled in our study. Inadequate platelet response to aspirin was defined as residual platelet aggregation>or=20% per arachidonic acid-induced light transmission aggregometry. Morning urinary samples were used to determine levels of isoprostanes (8-iso-PGF2alpha) using an enzyme immunoassay.
  
  
  RESULTS
  Eight subjects were deemed to present inadequate platelet response to aspirin. Wide intersubject variability was observed in urinary 8-iso-PGF2alpha levels. However, levels were similar between aspirin responders and non-responders. Patients with inadequate platelet response to aspirin had higher platelet counts and received the lowest daily aspirin dose when compared to responders, suggesting subtherapeutic aspirin therapy due to increased platelet production. Only platelet count remained independently predictive of inadequate platelet response to aspirin in a multiple logistic regression model.
  
  
  CONCLUSIONS
  Urinary 8-iso-PGF2alpha levels, a reflection of systemic oxidative stress, did not appear to contribute to impaired platelet responsiveness to aspirin, while increased platelet production may partly explain this phenomenon.
authors.affiliation: Faculty of Pharmacy, Université de Montréal, Research Center, Department of Pharmacy, Hôpital du Sacré-Coeur de Montréal, 5400, Boulevard Gouin Ouest Montréal, Quebec, Canada H4J 1C5.
authors.forename: Marie
authors.initials: M
authors.lastname: Lordkipanidzé
authors.forename: Jean G
authors.initials: JG
authors.lastname: Diodati
authors.forename: Jacques
authors.initials: J
authors.lastname: Turgeon
authors.forename: Erick
authors.initials: E
authors.lastname: Schampaert
authors.forename: Donald A
authors.initials: DA
authors.lastname: Palisaitis
authors.forename: Chantal
authors.initials: C
authors.lastname: Pharand
mesh_terms: D000368:Aged; D001241:Aspirin / Q000009:adverse effects*; D001792:Blood Platelets / Q000166:cytology / Q000187:drug effects*; D003324:Coronary Artery Disease / Q000188:drug therapy* / Q000453:epidemiology; D015237:Dinoprost / Q000031:analogs & derivatives / Q000652:urine; D004351:Drug Resistance; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D018384:Oxidative Stress / Q000502:physiology*; D010974:Platelet Aggregation / Q000187:drug effects; D010975:Platelet Aggregation Inhibitors / Q000009:adverse effects; D010976:Platelet Count; D012307:Risk Factors; D013923:Thromboembolism / Q000453:epidemiology / Q000517:prevention & control*; D017211:Treatment Failure
chemical_list: D010975:Platelet Aggregation Inhibitors; C075750:8-epi-prostaglandin F2alpha; D015237:Dinoprost; D001241:Aspirin