Penicillin G, a beta-Lactam antibiotic, induces abnormalities in platelet function, in part, by inhibiting platelet membrane receptors and, also, by inhibiting post-receptor biochemical events. The platelet surface is the primary site of exposure to the antibiotic. We therefore investigated the effect of penicillin on platelet function and on the surface expression of the membrane glycoproteins GPIb, GPIb-IX, GPIIb-IIIa and P-selectin by flow cytometry and monoclonal antibodies directed against these proteins. In initial studies, platelet concentrates exposed to penicillin (2-20mM) for 48 h showed irreversible inhibition of aggregation by thrombin (<0.4U/m1) in washed platelets after removal of the antibiotic. Brief exposure (15 min) to similar doses of penicillin also inhibited aggregation but it was reversible upon removal of the drug. Flow cytometric analysis using fluorescently-labelled monoclonal antibodies revealed that brief (15 min) exposure of washed platelets to 10mM penicillin inhibited the thrombin- modulated decrease in expression of GPIb and GPIb-IX and increase in expression of GPIIb-IIIa an P-selectin. Penicillin also inhibited the regulation of GPIb-IX and GPIIb-IIIa surface expression in platelets in plasma activated by thrombin and ADP. A portion of this study has been published (Sloand EM, Klein HG, Pastakia KB, Pierce P, Prodouz KN. Blood 1992:2022-2027). A second manuscript, submitted to J Lab Clin Med, is in press.
