What are three overarching questions you should ask when seeing a patient with suspected autoimmune hemolytic anemia (AIHA)?

• Is there hemolysis?
  • Reticulocyte count – increased
  • Lactate dehydrogenase (LDH) – may be normal or increased
  • Haptoglobin – reduced
  • Blood film – spherocytes, agglutination or polychromasia
  • Urinalysis/dipstick test positive for blood but urine microscopy negative for red cells – if hemolysis is intravascular, leading to hemoglobinuria.
  • Urinary hemosiderin – can be detected approximately 1 week after onset of intravascular hemolysis.
• Is the hemolysis autoimmune?
  • A positive direct antiglobulin test (DAT) suggests an immune etiology.
  • DAT should include monospecific anti-IgG and anti-C3d.
• What is the type of AIHA?
  • Warm AIHA
    • Caused by autoantibodies (usually IgG) that bind red cells optimally in vitro at 37°C.
    • When tested with anti-C3 and anti-IgG reagents, the DAT would be positive for: IgG only (35%), IgG + C3 (56%) or C3 only (9%).
    • AIHA can be considered warm when there is a consistent clinical picture and a DAT positive to IgG, C3 or both, when a clinically significant cold reactive antibody has been excluded.
  • Cold AIHA (Cold hemagglutinin disease, CHAD):
    • Caused by autoantibodies (usually IgM) that bind red cells optimally in vitro at 4°C.
    • DAT is usually positive for C3 only, 21–28% are also positive with IgG.
    • CHAD can be diagnosed in patients with AIHA and a DAT positive to C3 +/- IgG, with a consistent clinical picture and a high titer cold reactive antibody. The thermal amplitude may be considered as a supportive serological investigation where diagnostic uncertainty exists.

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