No abstract

Aspirin-resistant patients as a group have reduced response to clopidogrel. Furthermore, we have identified a unique group of dual drug-resistant patients who may be at increased risk for thrombotic complications after PCI.

The proportion of circulating RPs strongly correlates with response to antiplatelet therapy in patients with stable CAD. Large platelets exhibit increased reactivity despite dual antiplatelet therapy, compared with smaller platelets.

To cite this article: Guthikonda S, Lev EI, Patel R, DeLao T, Bergeron AL, Dong J-F, Kleiman NS. Reticulated platelets and uninhibited COX-1 and COX-2 decrease the antiplatelet effects of aspirin. J Thromb Haemost 2007; 5: 490-6.Summary. Background: The mechanisms for the variability in antiplatelet effects of aspirin are unclear. Immature (reticulated) platelets may modulate the antiplatelet effects of aspirin through uninhibited cyclooxygenase (COX)-1 and COX-2. Objectives: To evaluate the role of reticulated platelets in the antiplatelet effects of aspirin. Methods: Sixty healthy volunteers had platelet studies performed before and 24 h after a single 325-mg dose of aspirin. Platelet studies included light transmission aggregometry; P-selectin and integrin a IIb b 3 expression, and serum thromboxane B 2 (TxB 2 ) levels. Reticulated platelets and platelet COX-2 expression were measured using flow cytometry. Results: Subjects were divided into tertiles based on the percentage of reticulated platelets in whole blood. Baseline platelet aggregation to 1 lg mL )1 collagen, and postaspirin aggregations to 5 lM and 20 lM ADP and collagen, were greater in the upper than in the lower tertile of reticulated platelets. Stimulated P-selectin and integrin a IIb b 3 expression were also higher in the upper tertile both before and after aspirin. Platelet COX-2 expression was detected in 12 ± 7% (n ¼ 10) of platelets in the upper tertile, and in 7 ± 3% (n ¼ 12) of platelets in the lower two tertiles (P ¼ 0.03). Postaspirin serum TxB 2 levels were higher in the upper (5.5 ± 4 ng mL )1 ) than in the lower tertile (3.2 ± 2.5 ng mL )1 , P ¼ 0.03), and decreased even further with ex vivo additional COX-1 and COX-2 inhibition. The incidence of aspirin resistance ( ‡ 70% platelet aggregation to 5 lM ADP) was significantly higher in the upper tertile (45%) than in the lower tertile (5%, P < 0.0001). Conclusions: Reticulated platelets are associated with diminished antiplatelet effects of aspirin and increased aspirin resistance, possibly because of increased reactivity, and uninhibited COX-1 and COX-2 activity.

No abstract