Laboratory Evaluation of Immune Hemolytic Anemias

Immune hemolytic anemias are disorders characterized by the immune system targeting and destroying red blood cells (RBCs). These conditions are classified based on factors such as the type of antibody involved, the temperature when hemolysis occurs, and whether the hemolysis is extravascular or intravascular. The immune-mediated destruction of RBCs can occur through several mechanisms, including the production of autoantibodies against self-antigens on RBCs, alloantibodies directed against foreign antigens on transfused RBCs, or drug-induced antibodies that bind to RBCs or trigger complement activation. Immune hemolytic anemias are categorized into autoimmune, alloimmune, and drug-induced mechanisms, each with unique etiologies and pathophysiological processes. Autoimmune hemolytic anemias (AIHAs) include warm AIHA, cold agglutinin disease, and mixed-type AIHA. The most common form of AIHA is warm AIHA, which is mediated by immunoglobulin G (IgG) antibodies and is often associated with hematologic, autoimmune, and infectious conditions. Cold agglutinin disease involves IgM antibodies that react at cold temperatures, and paroxysmal cold hemoglobinuria features an IgG autoantibody causing hemolysis upon rewarming. Alloimmune hemolytic anemia occurs when alloantibodies attack foreign RBC antigens, typically following blood transfusions or during hemolytic disease of the newborn. Drug-induced immune hemolytic anemia (DIIHA) occurs when drug-induced antibodies bind to and destroy RBCs. Laboratory evaluation is crucial for diagnosing and managing immune hemolytic anemias. Diagnostic tests include complete blood count (CBC), haptoglobin, lactate dehydrogenase (LDH), reticulocyte count, bilirubin levels, and direct antiglobulin test (DAT) or indirect antiglobulin test. Peripheral blood smears, tests for cold agglutinins, Donath-Landsteiner antibodies, and other specialized tests are essential for accurate diagnosis.