Reticulated platelets and uninhibited COX‐1 and COX‐2 decrease the antiplatelet effects of aspirin

• Published in: Journal of thrombosis and haemostasis Vol. 5; no. 3; pp. 490 - 496
• Main Authors: GUTHIKONDA, S., LEV, E. I., PATEL, R., DELAO, T., BERGERON, A. L., DONG, J.‐F., KLEIMAN, N. S.
• Format: Journal Article
• Language: English
• Published: Oxford, UK Blackwell Publishing Ltd 01.03.2007
• Subjects: Adenosine Diphosphate; Administration, Oral; Adult; aspirin; Aspirin - pharmacology; Blood Platelets - drug effects; Blood Platelets - enzymology; Blood Platelets - metabolism; Collagen; COX‐2; Cyclooxygenase 1 - metabolism; Cyclooxygenase 2 - metabolism; Cyclooxygenase Inhibitors - administration & dosage; Cyclooxygenase Inhibitors - pharmacology; Drug Resistance; Female; Flow Cytometry; Humans; Male; Membrane Proteins - metabolism; P-Selectin - biosynthesis; Platelet Aggregation - drug effects; Platelet Aggregation Inhibitors - administration & dosage; Platelet Aggregation Inhibitors - pharmacology; Platelet Function Tests; Platelet Glycoprotein GPIIb-IIIa Complex - biosynthesis; Reference Values; reticulated platelets; Tablets, Enteric-Coated; thromboxane; Thromboxane B2 - blood
• ISSN: 1538-7933; 1538-7836; 1538-7836
• DOI: 10.1111/j.1538-7836.2007.02387.x

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 αIIbβ3 expression, and serum thromboxane B2 (TxB2) 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 μg mL−1 collagen, and postaspirin aggregations to 5 μm and 20 μm ADP and collagen, were greater in the upper than in the lower tertile of reticulated platelets. Stimulated P‐selectin and integrin αIIbβ3 expression were also higher in the upper tertile both before and after aspirin. Platelet COX‐2 expression was detected in 12 ± 7% (n = 10) of platelets in the upper tertile, and in 7 ± 3% (n = 12) of platelets in the lower two tertiles (P = 0.03). Postaspirin serum TxB2 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 = 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 μm 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.