The Journal of International Medical Research 1989; 17: 514 - 520 Effects of Ticlopidine and Indobufen on PlateletAggregation Induced by A23187 and Adrenaline in the Presence of Different Anticoagulants C. Cimminiello, M. Milani, T. Uberti, G. Arpaia and G. Bonfardeci 4th Medical Department, Atherothrombotic Pathology, San Carlo Borromeo General Hospital, Milan, Italy As Ca 2 + is known to playa fundamental role in platelet function, the effect of combining two platelet aggregating agents (adrenaline and the ionophore A23187) with different effects on Ca 2 + was studied at levels subthreshold for aggregation using platelet-rich plasma from eight atherosclerotic patients. Adrenaline lowered the A23187thresh- old required to induce aggregation. The effects of treating patients with the antiplatelet agents, indobufen and ticlopidine, on A23187and adrenaline induced aggregation of platelets prepared in hirudin or sodium citrate was also evaluated. Aggregation was also studied using platelets resuspended in Ca 2 +-free and Ca 2 +-enriched Tyrode solution. Before treatment hirudin treated platelet-rich plasma, which has physiological extraplatelet Ca 2 + levels, was more sensitive to A23187 and adrenaline than was citrated platelet-rich plasma, which has suppressed Ca 2 + levels. Ticlopidine significantly raised the concentra- tion 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 lIb - IlIa complex on the platelet membranes. Low levels of extracellular Ca 2 + and ticlopidine may act synergistically to reduce the aggregatory response of stimulated platelets. KEY WORDS: Calcium ions; A23187; ionophore; adrenaline; tic1opidine; indobufen; platelets. 514 Received for publication: 22 March 1989;accepted 11 April 1989. Address for correspondence: Dr C. Cimminiello, Via Stefmi 12,20100 Milan, Italy. INTRODUCTION T here is increasing evidence that Ca 2 + modulates several steps during platelet aggregation. 1 -3 This ion also plays an impor- tant role through its interaction with the © Copyright 1989by Cambridge Medical Publications Ltd