order for intravascular AIHA to be recognizable, it requires overwhelming complement activation, therefore most AIHA is extravascular – be it IgG- or IgM-mediated. AIHA cannot be attributed to any single autoantibody. To determine the autoantibody or autoantibodies present in a patient, the Coombs test, also known as the antiglobulin test, is performed. There are two types of Coombs tests, direct and indirect; more commonly, the direct antiglobulin test (DAT) is used. Classification of the antibodies is based on their activity at different temperatures and their etiology. Antibodies with high activity at physiological temperature (approximately 37 °C) are termed warm autoantibodies. Cold autoantibodies act best at temperatures of 0–4 °C. Patients with cold-type AIHA, therefore, have higher disease activity when body temperature falls into a hypothermic state. Usually, the antibody becomes active when it reaches the limbs, at which point it opsonizes RBCs. When these RBCs return to central regions, they are damaged by complement. Patients may present with one or both types of autoantibodies; if both are present, the disease is termed "mixed-type" AIHA. When DAT is performed, the typical presentations of AIHA are as follows. Warm-type AIHA shows a positive reaction with antisera to IgG antibodies with or without complement activation. Cases may also arise with complement alone or with IgA, IgM or a combination of these three antibody classes and complement. Cold-type AIHA usually reacts with antisera to complement and occasionally to the above antibodies. This is the case in both cold agglutinin disease and cold paroxysmal hematuria. In general, mixed warm and cold AIHA shows a positive reaction to IgG and complement, sometimes IgG alone, and sometimes complement alone. Mixed-type can, like the others, present unusually with positive reactions to other antisera. Diagnosis Diagnosis is made by first ruling out other causes of hemolytic anemia, such as G6PD, thalassemia, sickle-cell disease. Clinical history is also important to elucidate any underlying illness or medications that may have led to the disease. Laboratory investigations are carried out to determine the etiology of the disease. Following confirmation of hemolysis (seen with laboratory markers of low hemoglobin, elevated LDH, decreased haptoglobin, and elevated unconjugated bilirubin), a direct antiglobulin test (DAT)(also known as a Coomb's test) is done to show auto-immune pathogenesis with antibodies, compliment or both on the erythrocyte surface. This is followed by a monospecific DAT that identifies the specific antibody and compliment types on the erythrocyte surface. In cold