Platelet dysfunction induced by parenteral carbenicillin and ticarcillin. Studies of the dose-response relationship and mechanism of action in dogs

Abstract

Sequential studies of platelet function were performed in dogs receiving continuous intravenous carbenicillin (CARB) or ticarcillin (TIC). Dose- and time-dependent platelet dysfunction was uniformly observed during the administration of CARB or TIC, 250 to 1000 mg/kg/24 hr. ADP-induced primary and secondary platelet aggregation was markedly inhibited within 24 to 48 hours in dogs receiving 750 or 1000 mg/kg/24 hr, but maximum impairment of aggregation did not occur until 3 to 5 days in dogs receiving 250 or 500 mg/kg/24 hr. Platelet glass bead column retention was abnormal in all dogs studied, and platelet factor 3 availability was impaired in 91%. Collagen-induced platelet aggregation was consistently impaired and the bleeding time was prolonged only during the infusion of greater than or equal to 750 mg/kg/24 hr. Plasma fibrinogen concentrations and thrombin times remained normal. CARB and TIC infusions resulted in inhibition of 14C-serotonin release and slightly decreased platelet ADP, while serotonin, ATP, and ultrastructure remained unchanged. The mutual correction of abnormal platelet aggregation by mixing CARB or TIC platelets with aspirin-treated platelets suggested that CARB and TIC inhibited the platelet release reaction by a mechanism other than inhibition of platelet cyclo-oxygenase. The platelet inhibitory properties of CARB and TIC demonstrated in this study suggest that they may be useful antithrombotic agents.