Platelet count, not oxidative stress, may contribute to inadequate platelet inhibition by aspirin

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• 作者：Marie Lordkipanidzé ; Jean G. Diodati ; Jacques Turgeon ; Erick Schampaert ; Donald A. Palisaitis ; Chantal Phar
• 刊名：International Journal of Cardiology
• 出版年：2010
• 出版时间：6 August 2010
• 年：2010
• 卷：143
• 期：1
• 页码：43-50
• 全文大小：244 K

文摘

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 ≥ 20 % per arachidonic acid-induced light transmission aggregometry. Morning urinary samples were used to determine levels of isoprostanes (8-iso-PGF_2α) 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-PGF_2α 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-PGF_2α 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.