Autoimmune hemolytic anemias (AIHAs) are conditions characterized by the production of antibodies against one's own red blood cells (RBCs), which can be primary (of unknown cause) or secondary (associated with other diseases or infections). AIHAs are classified into several categories based on their features in the direct antiglobulin test (DAT). These categories include: 1. **Warm-antibody AIHA (wAIHA)**: Exhibits pan-reactive IgG autoantibodies recognizing band 3, with a positive DAT for IgG and/or C3d. Treatment involves glucocorticoids, steroid-sparing agents, IVIG, or monoclonal antibodies against CD20, CD38, or C1q. 2. **Cold-antibody AIHA**: Includes cold agglutinin syndrome (CAS) and cold agglutinin disease (CAD), with positive DAT only for C3d. Treatment focuses on keeping the patient warm, and may include monoclonal antibodies against C1q or C5. 3. **Mixed AIHA**: Also known as combined cold and warm AIHA, has a positive DAT for both IgG and C3d. Treatment approaches include those for wAIHA and cold AIHA. 4. **Paroxysmal cold hemoglobinuria (PCH)**: Positive DAT only for C3d, driven by a biphasic cold-reactive IgG antibody. Management may consider monoclonal antibodies against C1q or C5. 5. **Direct antiglobulin test-negative AIHA (DAT-neg AIHA)**: Due to low levels of IgG antibodies in the DAT, managed similarly to wAIHA. 6. **Drug-induced immune hemolytic anemia (DIHA)**: Presents as wAIHA with DAT IgG and/or C3d, and treatment involves stopping the inciting drug. 7. **Passenger lymphocyte syndrome**: Occurs after transplantation, caused by B-cells from the donor reacting with recipient RBCs. Diagnosis is made through the Donath–Landsteiner test. The review discusses the diagnosis, pathophysiology, and treatment of each type of AIHA, emphasizing the importance of the DAT in classification and the role of specific biomarkers. Treatment options range from glucocorticoids to monoclonal antibodies, complement inhibitors, and immunosuppressive agents, depending on the type and severity of the AIHA.Autoimmune hemolytic anemias (AIHAs) are conditions characterized by the production of antibodies against one's own red blood cells (RBCs), which can be primary (of unknown cause) or secondary (associated with other diseases or infections). AIHAs are classified into several categories based on their features in the direct antiglobulin test (DAT). These categories include: 1. **Warm-antibody AIHA (wAIHA)**: Exhibits pan-reactive IgG autoantibodies recognizing band 3, with a positive DAT for IgG and/or C3d. Treatment involves glucocorticoids, steroid-sparing agents, IVIG, or monoclonal antibodies against CD20, CD38, or C1q. 2. **Cold-antibody AIHA**: Includes cold agglutinin syndrome (CAS) and cold agglutinin disease (CAD), with positive DAT only for C3d. Treatment focuses on keeping the patient warm, and may include monoclonal antibodies against C1q or C5. 3. **Mixed AIHA**: Also known as combined cold and warm AIHA, has a positive DAT for both IgG and C3d. Treatment approaches include those for wAIHA and cold AIHA. 4. **Paroxysmal cold hemoglobinuria (PCH)**: Positive DAT only for C3d, driven by a biphasic cold-reactive IgG antibody. Management may consider monoclonal antibodies against C1q or C5. 5. **Direct antiglobulin test-negative AIHA (DAT-neg AIHA)**: Due to low levels of IgG antibodies in the DAT, managed similarly to wAIHA. 6. **Drug-induced immune hemolytic anemia (DIHA)**: Presents as wAIHA with DAT IgG and/or C3d, and treatment involves stopping the inciting drug. 7. **Passenger lymphocyte syndrome**: Occurs after transplantation, caused by B-cells from the donor reacting with recipient RBCs. Diagnosis is made through the Donath–Landsteiner test. The review discusses the diagnosis, pathophysiology, and treatment of each type of AIHA, emphasizing the importance of the DAT in classification and the role of specific biomarkers. Treatment options range from glucocorticoids to monoclonal antibodies, complement inhibitors, and immunosuppressive agents, depending on the type and severity of the AIHA.