Duration of the effect of aspirin on the synthesis of thromboxane by density subpopulations of rabbit platelets stimulated with thrombin.

The controversy concerning the relationship between platelet buoyant density and platelet age is unresolved. Our earlier results with rabbit platelets indicate that the most-dense subpopulations are enriched in young platelets and that some platelets become less dense as they age. Other investigators have concluded that platelets either do not change in density upon aging or become more dense. In the present experiments, rabbit platelets were separated on discontinuous gradients of Stractan. Most-dense platelets synthesized significantly more thromboxane B2 (TXB2) (1.27 ng per 10(6) platelets) in response to thrombin (0.75 U/mL) than did least-dense platelets (0.70 ng per 10(6) platelets), indicating that the arachidonate pathway in most-dense platelets is more active than in least-dense platelets. After aspirin administration to rabbits, most-dense platelets recovered their ability to synthesize thromboxane B2 significantly more quickly than did least-dense platelets. Because the platelet cyclooxygenase that is responsible for TXB2 formation is permanently inhibited by aspirin, it is only the new platelets entering the circulation that will be able to form TXB2. These results indicate that, at least in rabbits, the most-dense platelets are enriched in young platelets, and that platelets decrease in density as they age in the circulation.