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Autoimmune hemolytic anemia (AIHA) is a condition in which the immune system produces autoantibodies that target and destroy red blood cells (RBCs), leading to hemolysis. It can be primary (idiopathic) or secondary to other diseases or triggers.

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https://www.youtube.com/watch?v=eCSBPZRRu4o

Classification

AIHA is classified based on the thermal reactivity of the autoantibodies:

Etiology

• Primary (Idiopathic) – ~50% of cases
• Secondary causes:
  • Autoimmune diseases: Systemic lupus erythematosus (SLE)
  • Lymphoproliferative disorders: CLL, NHL
  • Infections: Mycoplasma pneumoniae (cold AIHA), EBV
  • Drugs: Penicillin, methyldopa, cephalosporins
  • Post-viral (children)

Clinical Features

• Symptoms of anemia: fatigue, pallor, dyspnea, tachycardia
• Jaundice, dark urine
• Splenomegaly (more in warm AIHA)
• Acrocyanosis or Raynaud phenomenon (in cold AIHA)

Diagnosis

Diagnostic procedure for AIHA:

![When diagnosing a patient with a new-onset haemolytic anaemia and autoimmune haemolytic anaemia (AIHA) is suspected, the diagnosis of AIHA relies on a multiple-step procedure, including first the analysis of the peripheral blood smear. When the blood smear shows no abnormalities or the presence of spherocytes (~40% of warm AIHAs (wAIHAs)) or spontaneous red blood cell (RBC) agglutinates (cold agglutinin disease or cold agglutinin syndrome, drug-induced immune haemolytic anaemia (DIIHA)), the next step is the direct antiglobulin test (DAT). A positive DAT confirms the diagnosis of AIHA and, in combination with the presence of cold agglutinin in the serum, a diagnosis of AIHA can be made. When DAT is negative, other causes of inherited and acquired haemolytic anaemias must be ruled out before considering the diagnosis of DAT-negative AIHA (~5% of all AIHAs). cAIHA, cold AIHA; EMA, extracellular membrane of band 3 protein by eosin-5’-maleimide; G6PD, glucose 6-phosphate dehydrogenase; PCH, paroxysmal cold haemoglobinuria; PK, pyruvate kinase; PNH, paroxysmal nocturnal haemoglobinuria. aFlow cytometry

Michel, M., Crickx, E., Fattizzo, B. et al. Autoimmune haemolytic anaemias. Nat Rev Dis Primers 10, 82 (2024). https://doi.org/10.1038/s41572-024-00566-2](attachment:749acee5-7071-4032-ab9d-dbec674412e9:41572_2024_566_Fig3_HTML.webp)

When diagnosing a patient with a new-onset haemolytic anaemia and autoimmune haemolytic anaemia (AIHA) is suspected, the diagnosis of AIHA relies on a multiple-step procedure, including first the analysis of the peripheral blood smear. When the blood smear shows no abnormalities or the presence of spherocytes (~40% of warm AIHAs (wAIHAs)) or spontaneous red blood cell (RBC) agglutinates (cold agglutinin disease or cold agglutinin syndrome, drug-induced immune haemolytic anaemia (DIIHA)), the next step is the direct antiglobulin test (DAT). A positive DAT confirms the diagnosis of AIHA and, in combination with the presence of cold agglutinin in the serum, a diagnosis of AIHA can be made. When DAT is negative, other causes of inherited and acquired haemolytic anaemias must be ruled out before considering the diagnosis of DAT-negative AIHA (~5% of all AIHAs). cAIHA, cold AIHA; EMA, extracellular membrane of band 3 protein by eosin-5’-maleimide; G6PD, glucose 6-phosphate dehydrogenase; PCH, paroxysmal cold haemoglobinuria; PK, pyruvate kinase; PNH, paroxysmal nocturnal haemoglobinuria. aFlow cytometry

Michel, M., Crickx, E., Fattizzo, B. et al. Autoimmune haemolytic anaemias. Nat Rev Dis Primers 10, 82 (2024). https://doi.org/10.1038/s41572-024-00566-2