Effects of Penicillin G and Cephalothin on Platelet Function in Vivo

Abstract

Penicillin G and related antibiotics have been shown by a number of investigators to inhibit platelet reactions in vitro (1-5). These antibiotics have also been reported to cause excessive bleeding in patients, and to increase the bleeding times in patients and volunteers receiving high doses of these drugs (1, 3-7).

In previous studies ((2), and Cazenave et al. Brit. J. Haematol., in press) we showed that penicillin G, carbenicillin, and cephalothin inhibit the adherence of platelets to a collagen-coated surface and to the damaged aortic surface of rabbits. We also found that penicillin G and cephalothin became associated with the platelets and that their inhibitory effects in vitro persisted after the platelets were washed and resuspended in fresh media.

Although the antibiotics have been shown to affect platelet function in vitro, it has not been established whether these antibiotics prolong the bleeding time in vivo by affecting the vessel wall, the plasma proteins, or the platelets. To investigate this question, we have treated platelets with penicillin G or cephalothin in vitro, washed the platelets, resuspended them in fresh media, reinfused them into thrombocytopenic rabbits, and examined their ability to shorten the prolonged bleeding times of these animals. We have also studied the effect of pretreatment of rabbit platelets with penicillin G, on platelet survival time upon infusion into rabbits.

Materials and methods. Reagents. Penicillin G (USP sodium, 1650 units/mg) was obtained from General Biochemicals, Chagrin Falls, Ohio). Cephalothin (Keflin) was a gift of Dr. R. S. Dolman, Eli Lilly and Co. (Canada), Toronto, Ontario. The antibiotics were dissolved in water at a concentration of 150 mM. Dilutions to the required concentrations were made with modified Tyrode solution (no calcium or magnesium); the pH was adjusted to 7.35 and the osmolarity to 290 mOsm.