Mixed warm and cold autoimmune hemolytic anemia (AIHA) runs a chronic course with severe, intermittent exacerbations. Therapeutic options for treatment of hemolysis associated with mixed AIHA are limited. There have been only two reported cases of effective use of rituximab in the treatment of mixed AIHA. We report a case of severe mixed AIHA that did not respond to steroids and responded to one cycle of rituximab. A 62-year-old male presented with dyspnea, jaundice and splenomegaly. Blood work revealed severe anemia (hemoglobin 4.9 g/dl) with biochemical evidence of hemolysis. Exposure to cold led to worsening of hemolysis and hemoglobinuria. Direct antiglobulin test was positive for IgG and complement (C3d); and cold agglutinins were detected. Bone marrow revealed erythroid hyperplasia. Positron emission tomography scan showed no sites of pathologic uptake. There was no other evidence of a lymphoid or myeloid disorder. Initial therapy consisted of avoidance of cold, intravenous methylprednisolone and a trial of plasmapheresis; however, there was no clinically significant response and the patient continued to be transfusion dependent. He was then started on intravenous rituximab 375 mg/m2/week. After two treatments, hemoglobin stabilized and transfusion requirement diminished.

Rituximab, continued for a total of four weeks, led to complete resolution of hemolytic anemia and associated symptoms. At his last visit, about 8 months after initial rituximab treatment patient continues to be in complete remission. This is the first reported case of mixed type AIHA not responding to steroid therapy with complete response to only one cycle of rituximab. Previous two reports of rituximab use in mixed AIHA have described initial brief response to steroids and the use of rituximab at the time of relapse. In both the cases, response to one cycle of rituximab was short-lived requiring a second cycle of rituximab. Our case demonstrates that severe hemolysis associated with mixed AIHA can be unresponsive to steroid therapy and a single cycle of rituximab may lead to prompt and durable complete remission. Rituximab is an effective treatment for mixed AIHA, especially when immediate response is desired, and merits further evaluation in this setting.

Author notes

Disclosure: No relevant conflicts of interest to declare.