Aspirin resistance among long-term aspirin users after carotid endarterectomy and controls: flow cytometric measurement of aspirin-induced platelet inhibition.

Abstract

BACKGROUND:

Numerous studies have indicated that some patient subpopulations do not respond to the antithrombotic effects of aspirin. The objective of this study was to evaluate aspirin-induced inhibition of platelet cyclooxygenase (COX) using a flow cytometric technique in long-term aspirin users after carotid endarterectomy (CEA) and controls with newly diagnosed carotid stenosis not taking aspirin and to compare these results with platelet function analyzer measurements.

METHODS:

The study included 86 patients with a history of CEA on long-term aspirin therapy (100 mg daily) and 29 age-matched patients with newly diagnosed carotid artery stenosis not taking aspirin. Platelet-rich plasma diluted with phosphate-buffered saline was incubated with arachidonic acid (ARA) at a final concentration of 80 micromol/L. After staining with phycoerythrin-labeled anti-P-selectin (CD62p) antibody, platelet CD62p-antigen expression was measured on a flow cytometer.

RESULTS:

Flow cytometric measurement of ARA-induced platelet activation showed an inhibition of ARA-induced platelet stimulation in all patients on aspirin therapy, whereas all but two controls (95%) showed expected platelet reactivity. In contrast, results of the platelet function analyzer measurements were normal in 16% of aspirin-treated patients.

CONCLUSIONS:

Flow cytometric measurement of CD62p expression on platelets after incubation with ARA proved to be a practicable tool to monitor aspirin-induced inhibition of platelet COX. Results in patients on long-term low-dose aspirin therapy show that the inability of aspirin to inhibit platelet COX for both symptomatic and asymptomatic patients with high-grade internal carotid artery stenosis is a very rare event. So-called aspirin resistance detected quite frequently by platelet function analyzer measurement is most likely from COX-independent mechanisms.

• Authors: Afshin Assadian, Jaqueline Lax, Ursula Meixner-Loicht, Georg W Hagmüller, Peter Michael Bayer, Wolfgang Hübl
• Journal: Journal of vascular surgery (J Vasc Surg) Vol. 45 Issue 6 Pg. 1142-7; discussion 1147 (Jun 2007) ISSN: 0741-5214 [Print] United States
• PMID: 17543677 (Publication Type: Comparative Study, Journal Article)

Chemical References

• Cyclooxygenase Inhibitors
• Fibrinolytic Agents
• P-Selectin
• Arachidonic Acid
• Prostaglandin-Endoperoxide Synthases
• Aspirin

Topics

• Aged
• Arachidonic Acid (pharmacology)
• Aspirin (pharmacology, therapeutic use)
• Blood Platelets (drug effects, enzymology, immunology)
• Carotid Stenosis (blood, drug therapy, surgery)
• Case-Control Studies
• Cyclooxygenase Inhibitors (pharmacology, therapeutic use)
• Drug Resistance
• Endarterectomy, Carotid
• Female
• Fibrinolytic Agents (pharmacology, therapeutic use)
• Flow Cytometry
• Humans
• Male
• P-Selectin (metabolism)
• Platelet Function Tests (methods)
• Prostaglandin-Endoperoxide Synthases (metabolism)
• Severity of Illness Index