Platelet count, not oxidative stress, may contribute to inadequate platelet inhibition by aspirin.
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.
Lordkipanidzé
Marie
M
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.
Diodati
Jean G
JG
Turgeon
Jacques
J
Schampaert
Erick
E
Palisaitis
Donald A
DA
Pharand
Chantal
C
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
D010975:Platelet Aggregation Inhibitors; C075750:8-epi-prostaglandin F2alpha; D015237:Dinoprost; D001241:Aspirin