Aspirin resistance among long-term aspirin users after carotid endarterectomy and controls: flow cytometric measurement of aspirin-induced platelet inhibition.
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.
Assadian
Afshin
A
Department of General and Vascular Surgery, Wilhelminenspital Vienna, Vienna, Austria. afshin_assadian@yahoo.de
Lax
Jaqueline
J
Meixner-Loicht
Ursula
U
Hagmüller
Georg W
GW
Bayer
Peter Michael
PM
Hübl
Wolfgang
W
D000368:Aged; D016718:Arachidonic Acid / Q000494:pharmacology; D001241:Aspirin / Q000494:pharmacology / Q000627:therapeutic use*; D001792:Blood Platelets / Q000187:drug effects* / Q000201:enzymology / Q000276:immunology; D016893:Carotid Stenosis / Q000097:blood / Q000188:drug therapy* / Q000601:surgery; D016022:Case-Control Studies; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology / Q000627:therapeutic use*; D004351:Drug Resistance; D016894:Endarterectomy, Carotid; D005260:Female; D005343:Fibrinolytic Agents / Q000494:pharmacology / Q000627:therapeutic use*; D005434:Flow Cytometry; D006801:Humans; D008297:Male; D019007:P-Selectin / Q000378:metabolism; D010979:Platelet Function Tests / Q000379:methods*; D011451:Prostaglandin-Endoperoxide Synthases / Q000378:metabolism; D012720:Severity of Illness Index
D016861:Cyclooxygenase Inhibitors; D005343:Fibrinolytic Agents; D019007:P-Selectin; D016718:Arachidonic Acid; D011451:Prostaglandin-Endoperoxide Synthases; D001241:Aspirin