19528 Background: Rituximab, an anti-CD20 monoclonal antibody, is a generally safe and well-tolerated drug. Severe acute thrombocytopenia following administration is a rare phenomenon. Case Report: An 84-year old male with a recent diagnosis of aggressive mantle cell lymphoma was admitted with a mild urinary tract infection. His condition gradually improved and inpatient chemotherapy was begun with R-CHOP. He received a 660 mg rituximab infusion without initial complication. The next day his platelet count had fallen from a pre-infusion level of 121,000/mm3 to 15,000/mm3. There were no signs of hemorrhage and over the course of the next three days the platelet count increased to 24,000. He did not require platelet transfusion and had a marked decrease in his white blood count and lymphadenopathy. The patient was discharged in good condition. Results: A MEDLINE/OVID database search revealed only five previous reported cases of rituximab-induced thrombocytopenia in adults. These included two cases of hairy cell leukemia, two cases of mantle cell lymphoma and one case of prolymphocytic leukemia. Pre-treatment platelet counts ranged from 31,000 to 151,000, and post-treatment counts from 6,000 to 10,000 (mean recorded drop 82,200). Four patients received platelet transfusions. Discussion: Rituximab-induced thrombocytopenia is likely underdiagnosed because most patients do not have blood counts performed the day after treatment. Proposed theories include; (i) CD20 antigen causing antigen-antibody immune-mediated cell lysis by compliment activation, (ii) CD20 antigen on the platelet surface, (iii) platelet binding of a soluble anti-CD20/rituximab complex, and (iv) intravascular fibrinolysis. Interestingly our case and all previously reported cases involved massive bone marrow involvement by neoplastic B-lymphocytes. A large number of patients treated with rituximab will have routine blood counts checked 1 to 2 weeks following therapy and physicians may wrongly attribute thrombocytopenia to the effects of other chemotherapy and make unnecessary dose reductions. Rituximab should therefore be used with caution, especially in those patients with bone marrow involvement. Routine blood counts should be considered soon after therapy to document this potential adverse effect. No significant financial relationships to disclose.