agglutinin disease with mild anemia with limited and compensated hemolysis can be monitored with adjunct supportive care (such as avoidance of cold exposure or thermal protection to prevent against hemolysis). Rituximab is used to treat pathogenic B-cell clones in cold agglutinin disease with response rates of 45-60%. Relapses are common upon discontinuation of rituximab, but the medication can be restarted to achieve subsequent remission. Rituximab can be combined with bendamustine to achieve a 71% overall and 40% complete response rate with an increased response seen with prolonged therapy (with a time to best response at a median of 30 months) due to the drugs' effect on long lived plasma cells. Splenectomy is less efficacious in cold agglutinin disease. Special considerations are required when treating people with AIHA using blood transfusion. In cold agglutinin disease; the patient and the extremity should be kept warm during transfusion to prevent agglutination and hemolysis of the donor and patient red blood cells. In warm AIHA; cross-matching of blood will show incompatibility so it is recommended to perform a bedside in vivo compatibility test prior to infusion. Erythropoietin (EPO) has been shown to increase hemoglobin levels in cold and warm AIHA. History "Blood-induced icterus" produced by the release of massive amounts of a coloring material from blood cells followed by the formation of bile was recognized and described by Vanlair and Voltaire Masius' in 1871. About 20 years later, Hayem distinguished between congenital hemolytic anemia and an acquired type of infectious icterus associated with chronic splenomegaly. In 1904, Donath and Landsteiner suggested a serum factor was responsible for hemolysis in paroxysmal cold hemoglobinuria. French investigators led by Chauffard stressed the importance of red-cell autoagglutination in patients with acquired hemolytic anemia. In 1930, Lederer and Brill described cases of acute hemolysis with rapid onset of anemia and rapid recovery after transfusion therapy. These hemolytic episodes were thought to be due to infectious agents. A clear distinction between congenital and acquired hemolytic anemia was not drawn, however, until Dameshek and Schwartz in 1938, and, in 1940, they demonstrated the presence of abnormal hemolysins in the sera of patients with acquired hemolytic anemia and postulated an immune mechanism. During the past three decades, studies defining red-cell blood groups and serum antibodies have produced diagnostic methods that have laid the basis for immunologic concepts relevant to many of the acquired hemolytic states. Of these developments, the antiglobulin test described