Defective platelet function following the administration of penicillin compounds

Platelet function and blood coagulation were studied in five human volunteers receiving penicillin-G in incremental doses of 1.2--48 million U/day, in six volunteers receiving ampicillin in incremental doses of 60--300 mg/kg/day (4--20 g/day), and in six volunteers receiving methicillin in incremental doses of 60--300 mg/kg/day. Coagulation tests remained normal in all 17 volunteers. However, ADP- induced platelet aggregation became abnormal in every subject except one receiving ampicillin and one receiving methicillin. Defective aggregation occurred with predictability with the following doses: penicillin-G, 24 million U/day; ampicillin, 300 mg/kg/day; methicillin, 300 mg/kg/day. All volunteers given penicillin-G and all given ampicillin experienced dose-related prolongation of bleeding time which did not occur with methicillin. Striking prolongation of bleeding time occurred only with penicillin-G in doses of 48 million U/day. Other tests of platelet function including clot retraction, platelet factor 3 availability, and collagen-induced or epinephrine-induced aggregation remained normal during the administration of these drugs. Measurement of intracellular adenine nucleotides revealed that the ADP and ATP content of platelets was unaffected. It appears that at least one mechanism by which the penicillin compounds alter platelet behavior is by interfering with activation of these cells by ADP.