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Cold antibody haemolytic anaemia

Last reviewed dd mmm yyyy. Last edited dd mmm yyyy

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Cold haemagglutin disease is a reactive autoimmune haemolytic associated with IgM antibodies to red blood cells. These antibodies react best at low temperature.

The majority of cases are idiopathic and present in patients over the age of 60 years.

Secondary causes of cold haemagglutinin disease include:

  • non-Hodgkin's lymphoma
  • Mycoplasma pneumoniae infection
  • infectious mononucleosis

The red cells become coated with IgM antibodies in the cooler peripheral circulation. Complement is activated when the blood warms up resulting in intravascular haemolysis.

IgM is detectable on the red cells at 4øC. At higher temperatures, IgM detaches from the red cell surface but complement can still be detected. Circulating free cold autoantibodies - cold agglutins - are also present in the patients serum. A direct Coombs' test may be positive with a reagent containing anti-complement antibodies.

Presentaton is usually with symptoms of chronic haemolytic anaemia i.e. jaundice, anaemia, haemoglobinuria, and severe Raynaud's phenomenon on exposure to cold.

Treatment is rarely necessary provided the patient keeps warm. Steroid treatment and splenectomy have little role as haemolysis is predominantly intravascular. Plasma exchange to remove circulating IgM may be used in severe cases.


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The content herein is provided for informational purposes and does not replace the need to apply professional clinical judgement when diagnosing or treating any medical condition. A licensed medical practitioner should be consulted for diagnosis and treatment of any and all medical conditions.

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