Autoimmune Hemolytic Anemia (AIHA) Resource Center

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 summary of ITP from diagnosis to treatment to ongoing management

AIHA affects individuals across all ages, but its presentation, underlying causes, clinical course, and management differ substantially from childhood through adulthood. Recognition of these age-related differences is essential to accurate diagnosis, appropriate treatment selection, and long-term care planning.

Pediatric AIHA
Children with AIHA, rarely found in this population, present with variable degrees of severity, with the most common form being wAIHA. Treatment is necessary, given that the condition is chronic. The rate of mortality is up to 4% in children due to the severity of their condition or the multiple types of treatment.

Adult AIHA
Also considered rare in adults, AIHA is most commonly diagnosed in adults above 40 years. While AIHA can occur at any age, the majority are diagnosed above 40 years. As comorbidities increase with age, older adults with wAHIA also face an increased risk of morbidity and mortality.

AIHA in Females
wAHIA disproportionately affects women in the adult population, with approximately two-thirds of diagnosed patients being female. This increased risk is largely driven by the higher prevalence of associated autoimmune conditions in women, particularly systemic lupus erythematosus (SLE), the most common cause of secondary wAIHA in adults. Among adult-only cohorts, women account for 61–71% of cases, a pattern that contrasts with pediatric populations, where males represent the majority of patients. In women, wAIHA most often presents later in life, with peak incidence between 60 and 70 years of age.

Section References

• Voulgaridou A, Kalfa TA. Autoimmune Hemolytic Anemia in the Pediatric Setting. J Clin Med. 2021; 10(2):216. https://pmc.ncbi.nlm.nih.gov/articles/PMC7828053/
• Jackson L, Zhdanava M, Pesa J, Boonmak P, Chen G, Liu D, Pilon D, Choudhry Z, Shah S. Mortality associated with warm autoimmune hemolytic anemia among Medicare beneficiaries. Blood. 2025; 146 (Supplement 1): 2694. doi: https://doi.org/10.1182/blood-2025-2694
• 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

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
Diagnosis of AIHA may be difficult in certain clinical settings, as the DAT is neither fully sensitive nor specific. Initial polyspecific DAT testing, which is commonly performed in transfusion services, may fail to detect some cases of AIHA, does not reliably distinguish wAIHA from CAD, and may be confounded by prior treatments such as transfusion or immunosuppression.

Additionally, the presence of concomitant hemolytic conditions may complicate or obscure the diagnosis of AIHA. Overlapping disorders, such as paroxysmal nocturnal hemoglobinuria (PNH), inborn errors of immunity, and bone marrow failure syndromes, can affect diagnostic interpretation and should be considered during evaluation.

Section References

• Tripathi AK, Chuda R. Laboratory Evaluation of Immune Hemolytic Anemias. [Updated 2024 Jul 9]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2025 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK606096/
• Theis SR, Hashmi MF. Coombs Test. [Updated 2022 Sep 12]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2025 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK547707/

Management of AIHA is guided by disease severity, etiology, comorbidities, and response to prior therapy. Treatment strategies are typically approached from first-line immunosuppression to targeted and immunomodulatory therapies for refractory disease.

First-line Therapy
Corticosteroids remain the cornerstone of initial treatment for wAIHA. Prednisone (or equivalent) is effective in rapidly controlling hemolysis in the majority of patients and is typically initiated at diagnosis.

Red blood cell transfusion may be required in cases of severe or life-threatening anemia, with careful compatibility testing. Identification and management of underlying or secondary causes—such as autoimmune disease, infection, or malignancy—are essential components of first-line care.

Suggested supplements: folic acid, B12, and iron.

Second-line Therapies
Immunosuppressive agents 
Rituximab

Third-line Therapy
Splenectomy

Additional Therapies (coming soon)

Section Resources

• Kuter DJ. Warm autoimmune hemolytic anemia and the best treatment strategies. Hematology Am Soc Hematol Educ Program. 2022; (1):105-113. https://pmc.ncbi.nlm.nih.gov/articles/PMC9821065/

Clinical trials are prospective studies in human participants designed to evaluate the safety, efficacy, and clinical utility of medical, surgical, or behavioral interventions. They are the primary mechanism for assessing new therapies, including drugs, devices, and lifestyle interventions. Trials may compare investigational approaches to the standard of care or evaluate strategies for early detection, prevention, and risk reduction. Some also focus on quality of life and patient-reported outcomes in chronic or life-threatening conditions.

ClinicalTrials.gov is a publicly accessible registry and results database of clinical studies conducted around the world, maintained by the U.S. National Library of Medicine.

Clinical Trials on AIHA Clinical Trials on wAIHA

Actively Recruiting Studies in the US:

• A Study to Investigate the Efficacy, Safety, and Pharmacokinetics of Oral Rilzabrutinib Compared With Placebo in Participants 18 Years of Age and Older With Warm Autoimmune Hemolytic Anemia (LUMINA 3)
• Cold Agglutinin Disease Real World Evidence Registry (CADENCE)
• Reduced Intensity Conditioning for Non-Malignant Disorders Undergoing UCBT, BMT or PBSCT (HSCT+RIC)

Patients need easy-to-navigate resources to help them get started in understanding this complicated disease. These curated resources are a useful place to help your patients along their AIHA management journey.

• wAIHA Warriors wAIHA Warriors is a patient support and advocacy organization designed to share resources and create a community for patients with wAIHA and the providers who treat them.
• Resources from Platelet Disorder Support Association (PDSA) on AIHA.
• Educational Resources for Patients with AIHA St. Jude’s Research Hospital has created patient resources to help navigate ongoing treatment and management, including discussion points to ask providers.
• Resources to Help Patients Live with Autoimmune Hemolytic Anemia, from Johns Hopkins University.
• Understanding AIHA and Its Treatment, from the Indiana Hemophilia & Thrombosis Center.
• Living with Autoimmune Hemolytic Anemia Understanding AIHA, its treatment, and how to improve quality of life.