Ristocetin * is a new antimicrobial agent consisting of two antibiotics, ristocetin A and B. These components have been separated from the fermentation broth of the actinomycete species Nocardia lurida. Advantages of this drug include the lack of development of resistant organisms and an absence of cross-resistance with other antibiotics. Several investigators have demonstrated the merit of ristocetin in problems of severe staphylococcal and enterococcal infections.1-4In previous publications5,6 the development of thrombocytopenia in four patients during ristocetin therapy was noted. Platelet depression was related to high doses of ristocetin and could be reversed by discontinuing or reducing the dose. Individuals with renal insufficiency were more susceptible to thrombocytopenia due to drug accumulation.The purpose of this publication is to report on the subsequent clinical experience and laboratory findings, and to relate these observations to the mechanism and site of action of ristocetin-induced thrombocyto-penia. Five patients have been treated with ristocetin since the previous publication. The dose was 25-50 mg. per kilogram of body weight to start, and 25-40 mg. per kilogram of body weight per day for main¬ tenance. In three there was no evidence of platelet depression or other hematological toxicity. Two patients developed thrombocytopenia, and their cases are included in this report. The remainder of this publica¬ tion deals with animal experiments and in vitro studies. MethodsAdult albino rabbits were given varying doses of ristocetin intravenously, using isotonic saline as the diluent in a volume of 5 milliliters. The drug was injected through the ear veins over a period of 3 to 5 minutes. Blood counts were ob¬ tained before and at varying periods after injection. Phase platelet counts were performed by the method of Brecher, Schneiderman, and Cronkite.7 Animals not injected with ristocetin were studied for possible daily variation of platelet counts, and no significant variation was noted. Isotonic saline and the antibiotics (penicillin and tetracycline) were injected in the same manner as ristocetin, and no significant adverse effects were noted. Bleeding time, clotting time, and clot retraction were evaluated in some experiments. Fibrinogen was determined by the method of Ratnoff and Menzie,8 fibrinolysin by the method of Adelson and Roeder."In vitro studies were performed, using blood from human donors who had not received risto¬ cetin, collected by venipuncture with disodium ethylene diamine tetra-acetic acid (EDTA) as a platelet preservative and anticoagulant. The blood was incubated in test tubes at 37 C for 30 minutes in serial dilutions of ristocetin from .075 mg. per ml. to 10 mg. per ml. The tubes were manually agitated every ten minutes during incubation, fol¬ lowing which platelet counts were determined.Penicillin, dihydrostreptomycin, and tetracycline,
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