agglutinin disease, the monospecific DAT is by definition positive for the compliment molecule C3d but IgM may be negative as the molecule may detach at the time of testing. The diagnosis of cold agglutinin disease is confirmed with an elevated cold agglutinin titer. A bone marrow biopsy is used in AIHA to identify a possible underlying lymphoproliferative disorder. Classification AIHA can be classified as warm autoimmune hemolytic anemia or cold autoimmune hemolytic anemia, which includes cold agglutinin disease and paroxysmal cold hemoglobinuria. These classifications are based on the characteristics of the autoantibodies involved in the pathogenesis of the disease. Each has a different underlying cause, management, and prognosis, making classification important when treating a patient with AIHA. Autoimmune hemolytic anemia Warm-antibody type Primary Secondary (lymphoproliferative disorders, autoimmune disorders) Cold-antibody type (anemia) Primary cold agglutinin disease Secondary cold agglutinin syndrome Associated with malignant disease Acute, transient, infection-associated (acute cold antibody mediated AIHA complicating Mycoplasma pneumoniae or viral infections) Chronic (lymphoproliferative disorders) Paroxysmal cold hemoglobinuria Idiopathic Secondary Acute, transient (Infections other than syphilis) Chronic (syphilis) Mixed cold- and warm-antibody type Idiopathic Secondary (lymphoproliferative disorders, autoimmune disorders) Drug-induced immune hemolytic anemia Autoimmune type Drug absorption type Neoantigen type Evidence for hemolysis The following findings may be present: Increased red cell breakdown Elevated serum bilirubin (unconjugated) Excess urinary urobilinogen Reduced plasma haptoglobin Raised serum lactic dehydrogenase (LDH) Hemosiderinuria Methemalbuminemia Spherocytosis Increased red cell production: Reticulocytosis Erythroid hyperplasia of the bone marrow Specific investigations Positive direct Coombs test Treatment Steroids are the first line treatment in warm AIHA; with oral prednisone achieving an 80% initial response rate, with a 30-40% sustained remission rate at 1 year. Steroids may be decreased at 3 weeks and tapered at 3–6 months depending on the response. Rituximab may be added to initial management to increase the response rate, or it may be used in cases of severe disease such as IgA mediated warm AIHA, mixed AIHA, Evans syndrome or in cases of high hemolysis levels). If a response cannot be achieved with steroids or rituximab, splenectomy can be done. Other third line options, that are less studied, include azathioprine, cyclophosphamide, cyclosporine, mycophenolate mofetil and bortezomib. The treatments for secondary warm AIHA are generally the same as primary warm AIHA, but with the addition of treating the underlying disease if possible. Steroids are not indicated in the treatment of cold agglutinin disease due to low response rates. Cases of cold