(Circulation. 1997;95:63-68.)
© 1997 American Heart Association, Inc.
Articles |
Prothrombotic Effects of Erythrocytes on Platelet Reactivity
Reduction by Aspirin
the Research Center and Department of Clinical Pathology, University Hospital La Fe, Valencia, Spain (M.T.S., J.V., J.A.), and the Divisions of Hematology and Medical Oncology and Departments of Medicine, Veterans Affairs Medical Center and Cornell University Medical College, New York, NY (A.J.M., M.J.B., L.B.S.).
Correspondence to Aaron J. Marcus, MD, Thrombosis Research Laboratory, Room 13028W, Department of Veterans Affairs Medical Center, 423 E 23rd St, New York, NY 10010-5050. E-mail mjbroek@mail.med.cornell.edu.
Background Aspirin effectively reduces the incidence of secondary vascular occlusive events in only 25% of patients. Low-dose aspirin as currently used blocks platelet production of prothrombotic thromboxane A2 and allows endothelial synthesis of antithrombotic prostacyclin. This regimen minimizes gastrointestinal toxicity. We previously showed that intact erythrocytes markedly enhance platelet reactivity. Therefore we investigated whether supplementation of low-dose aspirin with a single high dose at 2-week intervals could more effectively block erythrocyte promotion of platelet reactivity.
Methods and Results Effects of different aspirin regimens on erythrocyte enhancement of platelet reactivity in normal volunteers were measured with the use of an assay that evaluates both platelet activation and recruitment. After 15 days of daily ingestion of 50 mg aspirin, reactivity of platelets alone was inhibited. However, erythrocyte promotion of platelet activation and recruitment was only inhibited by 
50% and persisted in the total absence of thromboxane synthesis. In contrast, if 50 mg/d aspirin was preceded by a single loading dose of 500 mg aspirin, the erythrocyte prothrombotic effect was strongly inhibited (90%) for 2 to 3 weeks. However, over time, erythrocytes "escaped" from this inhibition, and once again became prothrombotic, even on a daily regimen of 50 mg aspirin.
Conclusions For clinical purposes, we recommend a loading dose of aspirin (500 mg), followed by daily administration of 50 mg. The loading dose should be repeated at 2-week intervals. This regimen blocks recovery of the erythrocyte capacity to promote platelet reactivity and may amplify the therapeutic potential of aspirin in cardiovascular disease.
Key Words: aspirin • platelets • thromboxane • thrombosis • erythrocytes • cardiovascular diseases
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