Effects of Ticlopidine and Indobufen on Platelet Aggregation Induced by A23187 and Adrenaline in the Presence of Different Anticoagulants

As Ca²⁺ is known to play a fundamental role in platelet function, the effect of combining two platelet aggregating agents (adrenaline and the ionophore A23187) with different effects on Ca²⁺ was studied at levels subthreshold for aggregation using platelet-rich plasma from eight atherosclerotic patients. Adrenaline lowered the A23187 threshold required to induce aggregation. The effects of treating patients with the antiplatelet agents, indobufen and ticlopidine, on A23187 and adrenaline induced aggregation of platelets prepared in hirudin or sodium citrate was also evaluated. Aggregation was also studied using platelets resuspended in Ca²⁺-free and Ca²⁺-enriched Tyrode solution. Before treatment hirudin treated platelet-rich plasma, which has physiological extraplatelet Ca²⁺ levels, was more sensitive to A23187 and adrenaline than was citrated platelet-rich plasma, which has suppressed Ca²⁺ levels. Ticlopidine significantly raised the concentration of A23187 required to induce aggregation in citrated but not hirudin treated platelet-rich plasma. Indobufen did not significantly affect A23187 induced aggregation. Ticlopidine acts by inhibiting the glycoprotein IIb – IIIa complex on the platelet membranes. Low levels of extracellular Ca²⁺ and ticlopidine may act synergistically to reduce the aggregatory response of stimulated platelets.