TP-9201, A GLYCOPROTEIN IIB IIIA PLATELET RECEPTOR ANTAGONIST, PREVENTS RETHROMBOSIS AFTER SUCCESSFUL ARTERIAL THROMBOLYSIS IN THE DOG/

Background and Purpose We examined the ability of TP-9201, a platelet glycoprotein IIb/IIIa receptor antagonist, to prevent carotid artery r ethrombosis in the anesthetized dog. Methods Occlusive thrombosis was induced by electrolytic injury of the left carotid artery. Thirty minu tes later, 0.05 U/kg of anisoylated plasminogen streptokinase activato r complex (APSAC) was infused locally to achieve clot lysis. Carotid a rtery recanalization was followed immediately by the infusion of eithe r saline (10 mL/h, 240 minutes; n=9), low-dose TP-9201 (120 mu g/kg pl us 3 mu g . kg(-1) . min(-1), 240 minutes; n=7), or high-dose TP-9201 (185 mu g/kg plus 5 mu g . kg(-1) . min(-1), 240 minutes; n=7). Ex viv o platelet aggregation responses to ADP or arachidonic acid were deter mined. Results TP-9201 produced complete inhibition of platelet aggreg ation in citrated platelet-rich plasma but a partial and dose-dependen t inhibition in heparinized platelet-rich plasma. A twofold and eightf old increase in the template bleeding time was associated with the inf usion of low-dose and high-dose TP-9201, respectively. There were freq uent cyclic flow reductions in both the saline and low-dose TP-9201-tr eated groups after thrombolysis. However, the high-dose TP-9201-treate d group exhibited a sustained Row with minimal evidence of cyclic flow reductions. At the conclusion of the protocol, patent vessels were fo und more frequently in the high-dose TP-9201 (5/7; P=.0048) than in th e low-dose TP-9201 treatment group (2/7; P=.17) when compared with the saline group (0/9). Infusion of high-dose TP-9201 was associated with a significant reduction in the thrombus mass as compared with the con trol vessels. Conclusions Administration of TP-9201 in conjunction wit h successful thrombolysis inhibited ex vivo platelet aggregation and p revented rethrombosis of the canine carotid artery. This study demonst rates that TP-9201, an inhibitor of the platelet GPIIb/IIIa receptor, can inhibit platelet-vessel wall interaction and thus prevent rethromb osis.