Evaluation of anti-platelet aggregatory effects of aspirin, cilostazol and ramatroban on platelet-rich plasma and whole blood.

To compare property in anti-platelet effects of aspirin (a cyclooxygenase inhibitor), cilostazol (a phosphodiesterase III inhibitor) and ramatroban (a specific thromboxane A2 receptor antagonist), we measured human platelet-rich plasma (PRP) aggregation induced by adenosine diphosphate (ADP), collagen and arachidonic acid, and whole blood (WB) aggregation induced by ADP. The release of P-selectin, transforming growth factor-beta 1, and the formation of thromboxane A2 in response to agonists were also investigated. Inhibitory effects of 100 micromol/l aspirin, 10 micromol/l cilostazol and 1 micromol/l ramatroban on 5 micromol/l ADP-induced PRP aggregation were similar. However, aspirin strongly inhibited thromboxane A2 formation in response to 5 micromol/l ADP compared with other drugs. Inhibitory effects of 10 micromol/l cilostazol on PRP aggregation and the release of molecules were quite similar in responsiveness induced by the three agonists. Aspirin and cilostazol inhibited platelet aggregation in a concentration-dependent, non-linear fashion, while ramatroban inhibited linearly with increasing concentration. Anti-platelet effects of drugs having different pharmacological mechanisms were demonstrated clearly by measuring PRP aggregation induced by the three agonists, and by measuring WB aggregation that most probably reflects not only platelet-platelet interactions, but also platelet-leukocyte interactions, as well as the release of intraplatelet molecules.