Guccione Ma

Effects of Penicillin G on Platelet Aggregation, Release, and Adherence to Collagen

Summary Penicillin G (1000–8000 units/ml) inhibits ADP, collagen or thrombin-induced platelet aggregation and the release reaction in human PRP and in suspensions of washed platelets from rabbits or pigs. Adherence of washed platelets from all three species to a collagen-coated surface is also inhibited by penicillin G in this concentration range. Penicillin G may coat platelets, as it does red cells, block the sites where the aggregating agents interact with the platelets, and thus inhibit the response of platelets to them. Since these concentrations are achieved in vivo when massive penicillin therapy is used or penicillin is applied locally, these observations may be relevant to alterations of platelet function during such treatment.

Effects of cephalothin and penicillin g on platelet function in vitro

High concentrations of cephalothin or penicillin G inhibit a number of the functions of human or rabbit platelets in citrated platelet‐rich plasma (PRP) and in suspensions of washed platelets. The reactions shown to be inhibited are: ADP‐induced shape change and the primary and secondary phases of aggregation and release induced by ADP or adrenaline in human citrated PRP; release and aggregation of washed human platelets exposed to collagen, thrombin, vasopressin, or the ionophore A23,187; aggregation of washed human platelets exposed to phytohaemagglutinin from Phaseolus vulgaris (PHA) or polylysine; release induced by concanavalin A or PHA in suspensions of washed platelets from rabbits; platelet adherence to a collagen‐coated surface or to the damaged intimal surface of the rabbit aorta; platelet factor 3 availability; lysis of rabbit platelets by an antiserum directed against them; and clot retraction. Neither antibiotic affected serotonin‐induced aggregation; a high concentration of cephalothin slightly inhibited the initial rate of serotonin uptake. Penicilloic acid showed about half the inhibitory effect of penicillin G on ADP‐induced aggregation. In citrated human platelet‐rich plasma, ampicillin and oxacillin inhibited ADP‐induced aggregation to the same extent as similar concentrations of penicillin G; in suspensions of washed platelets, however, ampicillin was less inhibitory than penicillin G or oxacillin. Platelet ultrastructure, assessed by transmission electron microscopy, was not visibly altered. Evidence that the antibiotics become bound to platelets is the finding that platelets incubated with the antibiotics and resuspended in fresh media showed less response to aggregating agents compared with control platelets. Penicillin G and related antibiotics may be inhibitory because they coat the platelet surface. Their effects on platelet functions are probably responsible for excessive bleeding and increased bleeding times observed in patients and volunteers receiving high doses of these antibiotics.