Effects of ticlopidine or ticlopidine plus aspirin on platelet aggregation and ATP release in normal volunteers: Why aspirin improves ticlopidine antiplatelet activity

Aspirin and ticlopidine are used to prevent arterial thrombosis. In some clinical settings ticlopidine is administered with aspirin for improving antithrombotic effect. We administered aspirin (100 mg/day), ticlopidine (500 mg/day), or ticlopidine and aspirin for 7 days to healthy volunteers. Platelet aggregation and ATP release induced by sodium arachidonate, ADP, or a combination of both were measured. Sodium arachidonate (0.25 mmol/L), which produces no platelet aggregation, combined with adenosine diphosphate (1 mu mol/L), which produced a reversible platelet aggregation of 20% after ticlopidine, resulted in a synergistic platelet aggregation response in normal (74.6 +/- 9.2%) and in ticlopidine platelet-rich plasma (59.1% +/- 14.9%, p < 0.0001). Synergism after sodium arachidonate (0.75 mmol/L) plus adenosine diphosphate (4 mu mol/L) fell from 75.8% +/- 11.0% and 59.1% +/- 15.6% after ticlopidine or aspirin, respectively, to 14.8% +/- 18.0% (p < 0.0001) after ticlopidine plus aspirin. Aspirin and ticlopidine alone did not inhibit adenosine triphosphate release as thoroughly as did aspirin plus ticlopidine. Aspirin or ticlopidine does not adequately prevent platelet activity as ticlopidine plus aspirin do. Addition of aspirin to treatment with ticlopidine improves their antiplatelet activity and better results could be obtained in arterial thrombotic prevention strategies.