What are the treatment guidelines for Autoimmune Hemolytic Anemia (AIHA)?

Treatment Guidelines for Autoimmune Hemolytic Anemia (AIHA)

First-line treatment for AIHA should be corticosteroids, with specific regimens based on AIHA subtype, followed by rituximab or splenectomy for refractory cases.

Classification and Diagnosis

AIHA is classified based on the thermal range of the autoantibody:

1. Warm AIHA (wAIHA):

   • DAT positive for IgG, C3d, or both
   • Antibodies react optimally at 37°C

2. Cold AIHA:

   • Cold agglutinin disease (CAD)
   • DAT positive for C3d only
   • Cold-reactive IgM antibodies

3. Mixed AIHA:

   • Features of both warm and cold AIHA
   • DAT positive for both IgG and C3d

4. Paroxysmal cold hemoglobinuria (PCH):

   • DAT positive for C3d
   • Biphasic cold-reactive IgG (Donath-Landsteiner test positive)

5. DAT-negative AIHA:

   • Clinical features of AIHA but negative DAT

Treatment Algorithm for AIHA

Warm AIHA (First-line)

1. Corticosteroids:

   • Prednisone/prednisolone 1 mg/kg/day PO for 4-6 weeks 1, 2, 3
   • Effective in 70-85% of patients
   • Slow taper over 6-12 months after response

2. Response assessment:

   • Clinical improvement expected within 2 weeks
   • Monitor hemoglobin, reticulocytes, LDH, and bilirubin

Cold Agglutinin Disease (First-line)

1. Rituximab:

   • Now recommended as first-line treatment 2, 3, 4
   • Standard dose: 375 mg/m² weekly for 4 weeks

2. Supportive measures:

   • Keep patient warm
   • Avoid cold exposure

Refractory/Relapsed Warm AIHA (Second-line)

1. Rituximab:

   • 375 mg/m² weekly for 4 weeks
   • Effective in 80-90% of cases 2
   • Increasingly preferred over splenectomy

2. Splenectomy:

   • Effective in approximately 70% of cases
   • Cure rate up to 20% 2, 3
   • Consider vaccination against encapsulated organisms before procedure

Third-line Options (for resistant/relapsing cases)

1. Immunosuppressive drugs:

   • Azathioprine (1-2 mg/kg/day)
   • Cyclophosphamide
   • Cyclosporine
   • Mycophenolate mofetil

2. Additional therapies:

   • Intravenous immunoglobulins (0.4-1 g/kg/day for 5 days)
   • Danazol
   • Plasma exchange (for severe cases)

3. Last resort options:

   • Alemtuzumab
   • High-dose cyclophosphamide

Monitoring and Follow-up

• Weekly CBC during initial treatment
• Monthly monitoring once stable
• Monitor for steroid side effects
• Long-term follow-up even after remission

Special Considerations

Acute Severe AIHA

For patients with severe hemolysis and life-threatening anemia:

• Consider high-dose intravenous methylprednisolone (1 g/day for 3 days)
• Blood transfusion may be necessary despite compatibility issues
• Consider plasma exchange in critical cases

Pregnancy

• Corticosteroids are first-line
• Avoid azathioprine if possible
• IVIG is relatively safe during pregnancy

Common Pitfalls and Caveats

1. Diagnostic challenges:

   • 5% of AIHA cases remain DAT-negative
   • Consider specialized testing for IgA autoantibodies, warm IgM, or low-affinity IgG

2. Treatment pitfalls:

   • Tapering corticosteroids too quickly leads to relapse
   • Inadequate duration of treatment (minimum 6 months recommended)
   • Failure to monitor for immunosuppression complications

3. Transfusion considerations:

   • Don't withhold transfusion in life-threatening anemia despite compatibility issues
   • Least incompatible units may be necessary

4. Secondary AIHA:

   • Always investigate for underlying conditions (lymphoproliferative disorders, autoimmune diseases, infections)
   • Treating the underlying condition may improve AIHA

The evidence strongly supports corticosteroids as first-line therapy for warm AIHA, with rituximab increasingly preferred as second-line treatment before splenectomy. For cold agglutinin disease, rituximab is now established as first-line therapy. Treatment should be continued for adequate duration with careful monitoring to prevent relapse and manage complications.