PLATELET DYSFUNCTION INDUCED BY PARENTERAL CARBENICILLIN AND TICARCILLIN - STUDIES OF DOSE-RESPONSE RELATIONSHIP AND MECHANISM OF ACTION IN DOGS

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  • 1 January 1978
    • journal article
    • research article
    • Vol. 91  (1) , 85-106
Abstract
Sequential studies of platelet function were performed in dogs receiving continuous i.v. carbenicillin (CARB) or ticarcillin (TIC). Dose- and time-dependent platelet dysfunction was uniformly observed during administration of CARB or TIC, 250-1000 mg/kg per 24 h. ADP-induced primary and secondary platelet aggregation was markedly inhibited within 24-48 h in dogs receiving 750 or 1000 mg/kg per 24 h, but maximum impairment of aggregation did not occur until 3-5 days in dogs receiving 250 or 500 mg/kg per 24 h. Platelet glass bead column retention was abnormal in all dogs studied; platlet factor 3 availability was impaired in 91%. Collagen-induced platelet aggregation was consistently impaired, and bleeding time was prolonged only during infusion of .gtoreq. 750 mg/kg per 24 h. Plasma fibrinogen concentrations and thrombin times remained normal. CARB and TIC infusions inhibited 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. Platelet inhibitory properties of CARB and TIC demonstrated suggest that they may be useful antithrombotic agents.