Autoimmune Hemolytic Anemia:Focusing on Therapy According to Classification

be classified according to the place of hemolysis as intravascular or extravascular.There are also other classifications according to underlying cause and type and thermal activity of the existing antibody as primary or secondary and warm or cold respectively.In this review, we focused on the treatment of AIHA according to classification. Classification According to underlying cause; primary or secondaryAIHAs can be subdivided according to underlying disease (Table 1).No underlying disease or agent can be distinguished in primary AIHA, whereas in the secondary cases, an associated condition is well documented such as autoimmune diseases, malignancies, infections or drugs.Malignancies are one of the most common causes.AIHA can be seen at the diagnosis or during the course of cancers such as lymphomas, Chronic Lymphocytic Leukemia (CLL), and solid tumors.AIHA can be also associated with autoimmune diseases particularly Systemic Lupus Erythematosus (SLE).Other examples of autoimmune diseases are antiphospholipid syndrome, Sjogren's syndrome, and rheumatoid arthritis [3][4][5][6][7].Beside these, many drugs can cause AIHAs [8,9].Secondary AIHAs are more challenging since the diagnosis and the treatment of the underlying cause is also necessary along with hemolysis.So the underlying causative agent and disease should be searched in details.According to the thermal activity of the antibody: warm, cold or mixed AIHA can also be classified as cold, warm or mixed according to type and optimal reactivity temperature of the auto-antibodies (Table 1).Warm AIHA (wAIHA) accounts for 80% of all AIHAs in adults.It is characterized by IgG type auto-antibodies that react with red blood cell antigens optimally at 37 0 C. The destruction of antibody coated red blood cells occurred at reticuloendothelial system especially in the spleen which is called extracellular hemolysis [10,11].As mentioned before, it can be subdivided as primary or secondary.In the primary or idiopathic form no Abstract AutoImmune Hemolytic Anemia (AIHA) is a rare disease characterized by premature destruction of the red blood cells due to autoantibodies produced against erythrocyte antigens.Early destruction shortens the lifespan of the erythrocytes and causes anemia, the hallmark of the disease.It is a heterogeneous disease so the clinical presentation is diverse from a mild asymptomatic anemia to a refractory disease associated with mortality and morbidity.The different classifications are constituted to determine the prognosis and appropriate treatment strategy.It can be classified according the absence or presence of an underlying cause as primary or secondary.Another classification in AIHA is according to the type and thermal activity of the antibody as Cold Agglutinin Disease (CAD) or warm AIHA.In CAD, rituximab monotherapy or combinations is the treatment of choice.In the warm AIHA, the steroid should be preferred as a first line therapy.In the steroid refractory or relapsed patients, rituximab or splenectomy can be chosen according to the patient's characteristics and the experience of the doctor.Since treatment mainly depends on the subtype of the disease differential diagnosis between the subtypes becomes important.This review will be focused on the classification and the treatment of AIHAs according to subtypes.