Treatment of Warm Autoimmune Hemolytic Anemia (AIHA)
Corticosteroids are the definitive first-line treatment for warm AIHA, with prednisone 1 mg/kg/day (or 0.5-1 mg/kg/day for moderate disease) achieving response in 70-85% of patients within 3 weeks. 1, 2, 3, 4
Treatment Algorithm Based on Disease Severity
Mild Disease (Hemoglobin <LLN to 10.0 g/dL)
- Close clinical follow-up with laboratory monitoring without immediate corticosteroid therapy 1, 2
- Monitor hemoglobin, reticulocyte count, bilirubin, LDH, and haptoglobin serially 2
Moderate Disease (Hemoglobin <10.0 to 8.0 g/dL)
- Initiate oral prednisone 0.5-1 mg/kg/day 1, 2
- This represents the threshold where corticosteroid therapy becomes necessary 1
Severe Disease (Hemoglobin <8.0 g/dL or Transfusion Required)
- Administer prednisone 1-2 mg/kg/day, with IV methylprednisolone (≥1 mg/kg daily) preferred for acute or severe presentations 1, 2
- Consider hospital admission for close monitoring 2
- Use minimum necessary RBC transfusion units for symptomatic patients 2
- Critical caveat: Avoid IV anti-D as it can exacerbate hemolysis 1, 2
Steroid Tapering Strategy
- Continue high-dose steroids for 3 weeks until clinical response is achieved 3
- Taper slowly over 6-12 months to minimize relapse risk 5
- Aim for complete normalization of hemoglobin and laboratory parameters 2
- Prolonged prednisone monotherapy >10 mg daily should be avoided due to well-known toxicities including weight gain, neuropsychiatric disorders, endocrine dysfunction, and cardiovascular events 3
Second-Line Treatment for Refractory or Relapsed Disease
Rituximab (375 mg/m² weekly for 4 weeks) has become the preferred second-line treatment with 70-80% effectiveness and is increasingly used before splenectomy. 1, 2, 4, 5
Alternative Second-Line Options
- Splenectomy: Effective in approximately 70% of cases with a presumed cure rate of 20% 4, 6, 5
- The choice between rituximab and splenectomy depends on surgical candidacy and patient preference 6
- Rituximab is particularly useful for steroid-refractory patients, those requiring high maintenance steroid doses, and unfavorable surgical candidates 6
Third-Line and Salvage Therapies
When both corticosteroids and rituximab/splenectomy fail, consider immunosuppressive agents:
- Cyclophosphamide 1-2 mg/kg/day 2, 4, 5
- Cyclosporine 3 mg/kg/day (adjusted for target trough levels 100-150 ng/mL) 2, 4, 5
- Azathioprine 4, 5, 7
- Mycophenolate mofetil 4, 5
Additional Therapeutic Options
- Intravenous immunoglobulin (IVIG) 0.3-0.5 g/kg for rapid but temporary improvement 2, 3, 5
- Danazol 3, 4, 5
- Last resort options: Plasma-exchange, high-dose cyclophosphamide, or alemtuzumab for severe refractory cases 3, 4, 5
Important Clinical Caveats
Monitoring Parameters
- Assess hemoglobin, reticulocyte count, bilirubin, LDH, haptoglobin, and direct antiglobulin test (DAT) regularly to evaluate treatment response 1, 2
- Monitor for steroid-related complications including glucose intolerance, hypertension, osteoporosis, and opportunistic infections 3
Transfusion Considerations
- Balance the risk of withholding RBC transfusions against possible benefits, particularly in critically ill patients 3
- Use minimum necessary units to avoid volume overload and alloimmunization 2