Diagnosis and treatment of autoimmune hemolytic anemia: classic approach and recent advances

which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited. Autoimmune hemolytic anemia (AIHA) is an uncommon disorder characterized by hemolysis mediated by autoanti-bodies directed against self-red blood cells (RBC), with the incidence of 1–3 per 100,000/year and mortality rate of approximately 11% [1, 2]. AIHA is classified as warm AIHA (caused mainly by warm-reactive IgG-mediated extravas-cular hemolysis, comprising 75% of all AIHA cases), cold AIHA (usually due to complement-mediated intravascular hemolysis, comprising about 15%), and mixed type AIHA (less than 5%), based on the thermal range of autoantibodies involved in the pathogenesis [3]. The laboratory diagnosis of AIHA depends on the result of direct antiglobulin test (DAT) which shows positivity with anti-IgG (usually in warm AIHA) and/or anti-C3d (usually in cold AIHA) antisera, and also the presence of laboratory findings supporting hemolysis such as increase of serum lactate dehydrogenase (LDH), reticulocytosis and spherocytosis in peripheral blood smears. However, since DAT may produce false negative results (up to 10% of all AIHA cases) due to IgA autoantibodies, low affinity IgG or RBC-bound IgG below the detection threshold of the test, it is important to understand that not all AIHA cases show positive DAT results. For more sensitive diagnosis of AIHA, the uses of mono-specific anti-IgA antisera/low ionic strength solutions (LISS) and application of more sensitive techniques such as column agglutination test or flow cytometry can be considered [2, 4, 5]. The presentation of clinical symptoms is typically insidious over several months but some patients show acute severe symptoms. Presenting complaints of AIHA depends on the severity of anemia itself, ranging from asymptomatic compensated reticulocytosis with mild hyperbilirubinemia to acute fulminant hemolysis leading to jaundice, hematos-plenomegaly, tachycardia and angina. Clinical features are determined by the presence of underlying diseases and degree of hemolysis, which depends on the autoantibody type. Patients with IgM warm-reactive AIHA are reported to have more severe hemolysis and higher death rates than those with other subtypes, and patients with cold AIHA tend to have more mild symptoms than those with warm AIHA [3]. The degree of anemia usually depends on the compensation represented by reticulocytosis and therefore, the patients with reticulocytopenia, which comprises 20% of adult and 39% of children patients with AIHA, would represent more severe clinical condition than those with reticulocytosis, and require strong RBC transfusion support [2, 6, 7]. The traditional treatment of warm AIHA was …