What is the treatment for autoimmune hemolytic anemia?

Treatment of Autoimmune Hemolytic Anemia

Corticosteroids are the first-line treatment for autoimmune hemolytic anemia, typically prednisone at 1-1.5 mg/kg/day, with addition of rituximab as second-line therapy for refractory cases. 1, 2

First-Line Treatment

• Prednisone 1-1.5 mg/kg/day orally is the standard initial therapy for warm antibody AIHA 1
• For severe or acute cases, high-dose intravenous methylprednisolone (≥1 mg/kg) should be administered as early as possible 3
• Treatment response should be monitored through hemoglobin levels, reticulocyte count, and direct antiglobulin test (DAT) 3
• Complete normalization of hemoglobin and other laboratory parameters should be the treatment goal 3

Treatment Algorithm Based on Severity

Grade 1 (Mild)

• Hemoglobin < lower limit of normal to 10.0 g/dL
• Continue close clinical follow-up with laboratory monitoring 3

Grade 2 (Moderate)

• Hemoglobin < 10.0 to 8.0 g/dL
• Administer prednisone 0.5-1 mg/kg/day 3
• Monitor response weekly initially, then every 2-4 weeks 1

Grade 3-4 (Severe)

• Hemoglobin < 8.0 g/dL or transfusion indicated
• Administer prednisone 1-2 mg/kg/day (oral or IV depending on symptoms) 3
• Consider hospital admission for close monitoring 3
• Consult hematology for specialized management 3
• Consider RBC transfusion for symptomatic patients (use minimum units necessary) 3

Second-Line Therapy for Refractory/Relapsed Cases

If inadequate response to corticosteroids after 2-3 weeks:

• Rituximab (375 mg/m² weekly for 4 weeks) has become the preferred second-line treatment with 70-80% effectiveness 3, 2
• Splenectomy is effective in approximately 70% of cases but is now less commonly used as first second-line option 2
• Intravenous immunoglobulin (IVIG) 0.3-0.5 g/kg can be used for rapid but temporary improvement 3

Third-Line and Beyond Options

For patients who fail second-line therapy:

• Immunosuppressive medications:

  • Azathioprine (1-2 mg/kg/day) 2
  • Cyclophosphamide (1-2 mg/kg/day) 3
  • Cyclosporine (3 mg/kg/day, adjusted for target trough levels between 100-150 ng/mL) 3, 4
  • Mycophenolate mofetil 2

• Combination therapy for steroid-refractory cases:

  • Rituximab + cyclophosphamide + dexamethasone has shown effectiveness in CLL-associated AIHA 5

• Salvage options for severe refractory cases:

  • Plasma exchange 1
  • High-dose cyclophosphamide 2
  • Alemtuzumab 2

Special Considerations

• Cold agglutinin disease: Rituximab is now recommended as first-line treatment rather than corticosteroids 2
• Secondary AIHA: Treat underlying condition in addition to AIHA-directed therapy 1
• Monitoring: Regular assessment of hemoglobin, reticulocyte count, bilirubin, LDH, and haptoglobin to evaluate response 3

Treatment Pitfalls and Caveats

• Establish clear criteria for adequate therapeutic response to avoid prolonged steroid exposure and associated side effects 1
• Patients receiving rituximab should be monitored for infusion reactions and increased risk of infections 2
• For patients undergoing splenectomy, vaccination against encapsulated organisms and prophylactic antibiotics are essential to prevent overwhelming post-splenectomy infection 1
• Patients with secondary AIHA (particularly associated with CLL) may have more refractory disease requiring more aggressive combination therapy 5