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American Journal of Pathology, Vol 91, 85-106, Copyright © 1978 by American Society for Investigative Pathology

REGULAR ARTICLES

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

GJ Johnson, GH Rao and JG White

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.




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Copyright © 1978 by the American Society for Investigative Pathology.