What is the management of autoimmune hemolytic anemia?

Management of Autoimmune Hemolytic Anemia

Initial treatment for autoimmune hemolytic anemia should begin with prednisone 1-2 mg/kg/day orally and folic acid 1 mg daily supplementation. 1

Diagnostic Evaluation

Before initiating treatment, a thorough diagnostic workup is essential:

• Complete blood count with peripheral smear
• Direct and indirect antiglobulin testing (Coombs test)
• Reticulocyte count
• Hemolysis markers (LDH, haptoglobin, bilirubin)
• Evaluation for underlying causes:
  • Infections (EBV, CMV, HIV, hepatitis)
  • Malignancies (CT scan of chest, abdomen, pelvis or PET-CT)
  • Autoimmune disorders (ANA, anti-dsDNA, complement levels)
  • Medication review for drug-induced hemolysis

Treatment Algorithm

First-Line Therapy

1. Prednisone 1-2 mg/kg/day orally 1

   • Continue until hemoglobin stabilizes and hemolysis markers improve
   • Then taper gradually based on clinical response
   • Weekly monitoring of CBC, reticulocyte count, and hemolysis markers

2. Supportive Care

   • Folic acid 1 mg daily to support increased erythropoiesis 1
   • Thromboprophylaxis with LMWH for hospitalized patients

Management of Severe Hemolysis

• RBC transfusion to target Hgb 7-8 g/dL (with notification to blood bank about immune hemolysis) 1
• Consider plasmapheresis in life-threatening cases

Second-Line Therapy (for steroid-refractory cases)

If no response after 1-2 weeks of prednisone or if prednisone doses >15 mg daily are required to maintain remission:

1. Rituximab 375 mg/m² weekly for 4 weeks 2, 1

   • Particularly effective in cold agglutinin disease

2. Alternative options:

   • Cyclophosphamide (1-2 mg/kg/day) 2
   • Combination of rituximab and cyclophosphamide for at least 5 weeks 2
   • Cyclosporine A 1, 3
   • Mycophenolate mofetil 1
   • IVIG 1

3. Splenectomy - consider for warm AIHA cases refractory to medical therapy 4

Special Considerations

Type-Specific Management

• Warm AIHA: Corticosteroids as first-line; add rituximab early in severe cases 5
• Cold Agglutinin Disease: Rituximab with or without bendamustine as first-line 5
• Mixed AIHA: Treatment approaches inclusive of those for both warm and cold AIHA 6

Immune Checkpoint Inhibitor-Related AIHA

For patients with AIHA due to immune checkpoint inhibitors:

• Grade 3-4: Permanently discontinue immune checkpoint inhibitor
• Hospital admission and hematology consultation
• Prednisone 1-2 mg/kg/day ± rituximab and/or cyclophosphamide 2
• If worsening or no improvement, add cyclosporine or immunosuppression/immunoadsorption 2

Monitoring and Follow-up

• Weekly CBC, reticulocyte count, and hemolysis markers during active treatment
• Regular monitoring of treatment-related side effects
• Assess for relapse after tapering or discontinuing therapy

Pitfalls and Caveats

• Blood transfusions should be used cautiously and only as temporary palliation in life-threatening situations 4
• Always notify the blood bank about immune hemolysis before transfusion
• Relapses may occur after steroid tapering or discontinuation
• Patients with extranodal disease often don't demonstrate durable responses to steroids alone 2
• Patients with hemolysis have increased thrombotic risk even when not on active treatment 1

The management of AIHA requires a systematic approach with prompt initiation of appropriate therapy based on the type of antibody involved and severity of hemolysis. Early consultation with hematology is recommended for optimal management.