We report a case of Thrombotic Thrombocytopenic Purpura occurring as an allergic response to trimethoprim-sulfamethoxazole therapy (Bactrim, Septra) in a Jehovah's Witness patient. The patient presented with fulminant microangiopathic hemolytic anemia and thrombocytopenia within 48 hr of initiating therapy with trimethoprim-sulfamethoxazole. Other symptoms of drug hypersensitivity included nausea, vomiting, urticarial rash, and leukopenia. Because of her religious faith, the patient was supported without plasma therapy with use of intravenous immunoglobulin, steroids, rituximab, and erythropoietin.