Autoimmune haemolytic anaemia

Autoimmune haemolytic anaemia (AHIA) is a haemolytic anaemia that occurs due to the body producing autoantibodies against its own RBCs. We distinguish two types of AHIA based on which temperature the autoantibodies best bind to the RBCs. In warm AIHA, also called warm agglutinin disease, the autoantibodies bind more strongly to the RBCs at body temperature (37°C). In cold AIHA, also called cold agglutinin disease, the autoantibodies bind to the RBCs more strongly in lower temperatures. The autoantibodies are called warm agglutinins and cold agglutinins, respectively.

Cold agglutinin disease

Cold agglutinin disease can be idiopathic (especially in elderly women) or it can be secondary to lymphoma, CLL or mycoplasma infection. The cold agglutinins are of IgM type and bind most strongly to RBCs at 4°C, but they bind at higher temperatures too. The warmest temperature the antibodies will bind to RBCs at varies from person to person; most clinically significant cold agglutinins bind to RBCs at around 28 degrees.

The periphery of the body can easily reach 28 degrees and so patients can experience haemolysis all the time. Cold obviously makes the symptoms worse as more autoantibodies bind to RBCs.

Warm agglutinin disease

Warm agglutinin disease can be idiopathic but is secondary in 2/3 of cases. It can be secondary to lymphoid neoplasms, solid tumors, autoimmune diseases and certain drugs, especially methyldopa. The warm agglutinins are of IgG type.

Pathophysiology

When autoantibodies bind to the RBCs the complement system is activated. This forms the membrane attack complex (MAC), which causes intravascular haemolysis. The opsonized RBCs are haemolysed in the spleen, which causes extravascular haemolysis. Intravascular haemolysis is only characteristic for cold agglutinin disease while extravascular haemolysis occurs in both.

Clinical features

Cold agglutinin disease:

• Acrocyanosis
• Splenomegaly
• Features of anaemia, especially pallor

Warm agglutinin disease:

• Features of anaemia, especially pallor
• Jaundice
• Splenomegaly

Diagnosis and evaluation

• Laboratory findings
  • Signs of haemolysis
• Peripheral blood smear
  • Normochromic anaemia
  • Anisocytosis
  • Autoagglutination
  • Polychromasia (RBCs that stain both basophilic and eosinophilic)
• Positive direct Coombs test
• Detection of cold agglutinins
  • Only in cold agglutinin disease of course

Treatment

The underlying cause, if any, should be treated. Corticosteroids or rituximab can improve the symptoms. People with cold agglutinin disease should avoid low temperatures.