Vancomycin-induced thrombocytopenia without isolation of a drug-dependent antibody

Vancomycin is a glycopeptide antibiotic used in the treatment of gram-positive infections including methicillin-resistant Staphylococcus aureus (MRSA). The most common adverse reaction to vancomycin is red man syndrome, which is a histaminergic reaction causing a rash on the upper torso, neck, and face after rapid infusion of the drug. Less commonly, vancomycin has been associated with thrombocytopenia. The etiology is believed to be the induction of drug-dependent antibodies, which in turn cause immune-mediated destruction of platelets. We describe a 41-year-old man who received two courses of vancomycin for the treatment of MRSA pneumonia and then experienced a decline in platelet count to a nadir of 15 x 10³/mm³. Vancomycin was discontinued, doxycycline was started, and the patient's platelet count rebounded over the next 6 days. The patient was readmitted to the hospital 2 months later for MRSA bacteremia and was rechallenged with vancomycin. He again experienced a decline in platelet count. Vancomycin was discontinued, and daptomycin was started. The patient's platelet count rebounded to normal levels over the next 5 days. Although the patient experienced acute thrombocytopenia after vancomycin exposure, no bleeding complications occurred, and the patient's platelet count rebounded to normal after the discontinuation of vancomycin. The patient had no other known risk factors for the development of rapid thrombocytopenia. Use of the Naranjo adverse drug reaction probability scale indicated a definite relationship (score of 9) between the patient's development of thrombocytopenia and vancomycin therapy. Although vancomycin was the presumed cause of thrombocytopenia in this patient, no drug-dependent antibody was isolated from blood samples collected after both exposures to vancomycin (analyzed by using a screening assay to identify drug-dependent antibodies to vancomycin [developed by the BloodCenter of Wisconsin]). Although the evidence supporting vancomycin induction of antibody-mediated destruction of platelets was lacking, further studies delineating alternate mechanisms of platelet destruction are warranted. Therefore, even in the absence of a positive antibody test, vancomycin should still be considered in the differential diagnosis as a cause of drug-induced thrombocytopenia.