A New Complement Inhibitor Shows Promise for Hard-to-Treat Autoimmune Hemolytic Anemia
A March 2025 case report describes how iptacopan, a new complement pathway inhibitor, achieved rapid improvement in a patient with severe wa...
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Autoimmune Hemolytic Anemia (AIHA)
Also known as: Acquired hemolytic anemia, Immune hemolytic anemia, Warm autoimmune hemolytic anemia (WAIHA), Cold agglutinin disease (CAD)
Primary organ/tissue: Blood (red blood cells); Spleen (site of destruction for warm AIHA); Liver
Overview
Autoimmune Hemolytic Anemia (AIHA) is a rare autoimmune condition in which the body's immune system mistakenly produces antibodies that attack and destroy its own red blood cells (RBCs). This destruction leads to anemia, meaning the blood cannot carry enough oxygen to tissues. AIHA may occur on its own (primary) or as a result of another disease (secondary), such as lupus, lymphoma, or certain infections.
Symptoms
General symptoms of anemia: Fatigue, Pale or yellowish skin (jaundice), Shortness of breath, Rapid heartbeat or palpitations, Dizziness or lightheadedness, Dark-colored urine. Cold AIHA-specific: Numbness or pain in fingers or toes when exposed to cold, Bluish discoloration (cyanosis) in extremities, Worsening symptoms in cold weather. Warm AIHA-specific: Often more acute onset, Fever, Enlarged spleen.
Causes
Primary AIHA: Idiopathic (no known cause, most cases of warm AIHA). Secondary AIHA: Autoimmune diseases (e.g., SLE, rheumatoid arthritis), Lymphomas and leukemias, Infections (e.g., Mycoplasma pneumoniae, EBV), Medications (e.g., penicillin, methyldopa).
Diagnosis
Complete blood count (CBC): Shows anemia, elevated reticulocytes; Peripheral blood smear: May show spherocytes or agglutination; Direct antiglobulin test (Coombs test): Confirms the presence of antibodies on RBCs; Lactate dehydrogenase (LDH): Elevated; Haptoglobin: Low; Bilirubin (indirect): Elevated.
Treatment
Warm AIHA: First-line: Corticosteroids (e.g., prednisone); Second-line: Immunosuppressants (azathioprine, rituximab), splenectomy; Supportive: Blood transfusions. Cold AIHA: Avoid cold exposure; Rituximab; Sometimes plasmapheresis or immunosuppressants.
Prognosis
Many cases respond well to treatment, particularly warm AIHA. Some patients may relapse or require long-term immunosuppression. Cold agglutinin disease is often chronic and relapsing. Early diagnosis and proper management lead to good long-term outcomes for most.
Prevalence
Estimated 1-3 cases per 100,000 people per year. More common in females and older adults. Warm AIHA accounts for about 70-80% of all cases.
Autoantibodies
| Autoantibody | Notes |
|---|---|
| IgG antibodies | Warm AIHA |
| IgM antibodies | Cold AIHA |
| Complement proteins (e.g., C3) |
Citations
- Barcellini W, Fattizzo B. Clinical Applications of Hemolytic Markers in the Differential Diagnosis and Management of Hemolytic Anemia. Dis Markers. 2015.
- Berentsen S. How I manage patients with cold agglutinin disease. Blood. 2021;137(10):1295-1303.
- Jager U, et al. Diagnosis and treatment of autoimmune hemolytic anemia in adults: Recommendations from the First International Consensus Meeting. Blood Rev. 2020.