Autoimmune hemolytic anemia

Differential Diagnosis

• Cold AIHA
  • Primary: cold agglutinin disease (CAD)
  • Secondary
    • Viral infections: EBV, CMV, others
    • Other infections: Mycoplasma (paroxysmal cold hemoglobinuria)
    • Other diseases: Waldenström macroglobulinema, lymphoma
    • Drugs: lenalidomide
• Warm AIHA
  • Primary: warm AIHA
  • Secondary
    • Viral infections: HIV, vaccines
    • Other diseases: lupus, CLL and other malignancies, chronic inflammatory disorders (including IBD)
    • Allogeneic hematopoietic stem cell transplantation
    • Drugs: cefotetan, ceftriaxone, piperacillin, immune checkpoint-modulating drugs (e.g. nivolumab)
• Drug-related
  • Penicillin
  • Methyldopa

Management

Warm AIHA

• Can be an emergency if severe and acute
• If life-threatening, transfuse ABO-matched but incompatible blood, thereby sparing the patient's own cells
• First-line: prednisone 1 mg/kg daily (response in 50% of patients)
• Second-line: rituximab 100 mg/week for 4 weeks, with prednisone
• Refractory: splenectomy

Cold agglutinin disease

• Chronic hemolysis in older patients caused by IgM antibodies produced by a B-lymphocyte clone (can show up as MGUS), therefore is essentially a form of Waldenström macroglobulinema
• First-line: rituximab ± fludarabine
• Prednisone and splenectomy are not helpful