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Autoimmune hemolytic anemia (AIHA) is an autoimmune disorder resulting in the production of antibodies directed against red blood cell antigens, causing shortened erythrocyte survival. The disorder is an acquired hemolysis and can be idiopathic or secondary to other autoimmune disorders, malignancies, or infections.

AIHA is based on the thermal range of the autoantibodies. The subtypes can be classified as either warm type (wAIHA) – the majority of AIHA cases, cold type (cold agglutinin disease (CAD)), or a rarer mixed warm and cold type.

• Warm Autoimmune Hemolytic Anemia (wAIHA) is the most common form of AIHA, representing 60-70% of all cases, and disproportionally affects women. It is most often characterized by having a gamma immunoglobulin (IgG) antibody that binds to red blood cell antigens independently of temperature.
• Cold Autoimmune Hemolytic Anemia, or cold agglutinin disease (CAD), is most commonly caused by immunoglobulin M (IgM), a cold-reactive autoantibody that binds to red blood cells at lower temperatures, leading to red cell agglutination in cooler areas of the body and activation of the complement system. CAD is reported to account for 20-25% of all AIHA cases.
• Mixed-type Autoimmune Hemolytic Anemia, (mAIHA) is a rare and complex form of AIHA, accounting for fewer than 10% of AIHA cases. It is characterized by the presence of both warm (IgG) and cold (IgM) reactive autoantibodies.

AIHA can be further classified as either primary (idiopathic) or secondary. Primary AIHA occurs in the absence of an identifiable underlying disorder and accounts for the majority of cases, estimated at more than 60%. Secondary AIHA may occur due to many underlying medical disorders, including autoimmune illnesses, blood malignancies, and infections, including coronavirus disease 2019 (COVID-19).

Section Resources:

• Tranekær S, Hansen DL, Frederiksen H. Epidemiology of Secondary Warm Autoimmune Haemolytic Anaemia—A Systematic Review and Meta-Analysis. Journal of Clinical Medicine. 2021; 10(6):1244. https://doi.org/10.3390/jcm10061244
• Despotovic JM, Kim TO. Cold AIHA and the best treatment strategies. Hematology Am Soc Hematol Educ Program. 2022; 2022 (1):90-95. https://pmc.ncbi.nlm.nih.gov/articles/PMC9821124/
• Branch DR. Warm autoimmune hemolytic anemia: new insights and hypotheses. Curr Opin Hematol. 2023; 30(6):203-209. https://pmc.ncbi.nlm.nih.gov/articles/PMC10552839/
• Berentsen S. Diagnosis and management of cold agglutinin disease. Hematology Am Soc Hematol Educ Program. 2025; 2025 (1): 295–304. doi: https://doi.org/10.1182/hematology.2025000718
• Barcellini W, Fattizzo B. The Changing Landscape of Autoimmune Hemolytic Anemia. Front Immunol. 2020;11:946. https://pmc.ncbi.nlm.nih.gov/articles/PMC7325906/
• Versino F, Pedone GL, Bortolotti M, Barcellini W, Fattizzo B. Mixed Type Autoimmune Hemolytic Anemia: A Single Center Observational Study. Blood. 2024; 144 (Supplement 1): 3844. doi: https://doi.org/10.1182/blood-2024-194219
• Jacobs JW, Raza S, Clark LM, et al. Mixed Autoimmune Hemolytic Anemia: A Systematic Review of Epidemiology, Clinical Characteristics, Therapies, and Outcomes. Am J Hematol. 2025;100(8):1397-1407. https://pmc.ncbi.nlm.nih.gov/articles/PMC12232602/
• Loriamini M, Cserti-Gazdewich C, Branch DR. Autoimmune Hemolytic Anemias: Classifications, Pathophysiology, Diagnoses and Management. Int J Mol Sci. 2024; 25(8):4296. https://pmc.ncbi.nlm.nih.gov/articles/PMC11049952/

Other Tools

• International Consensus Report on AIHA: Provider-driven medical summary on the treatment and management of AIHA, drawn from physicians worldwide
• New England Journal of Medicine Treatment Guide on AIHA: The NEJM has curated a set of resources for providers
• CDC’s NHLBI Autoimmune Hemolytic Anemia Resource Center: The CDC’s NHLBI collected resources of evergreen information for a good primer for providers
• Autoimmune Hemolytic Anemia in Emergency Medicine Questions & Answers: Medscape features a short summary of ITP from diagnosis to treatment to ongoing management

Healthcare professionals, especially those outside hematology, may have knowledge and practice gaps in the appropriate diagnosis of AIHA, given that the diagnosis is based on a set of highly specific biological changes and a positive direct Coombs test. Because the course of the disorder varies across populations and may be chronic or idiopathic, the treatment protocols may also vary, but primarily involve immune modulation with corticosteroids and other agents, including a growing focus on complement inhibitors.

Diagnostic Tests

• Complete Blood Count
• Haptoglobin
• Lactate Dehydrogenase
• Reticulocyte Count (not a percent)
• Bilirubin
• Peripheral Smear
• Direct Antiglobulin Testing (DAT), also known as the Coombs test, is a laboratory procedure used to detect the presence of antibodies against circulating red blood cells that induce hemolysis.

Diagnostic Challenges

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