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Genetic and Rare Diseases Information Center (GARD)

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Cold agglutinin disease

Other Names for this Disease
  • Anemia, hemolytic, cold antibody
  • CAD
  • Cold antibody disease
  • Cold antibody hemolytic anemia
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What are the signs and symptoms of cold agglutinin disease?

The blood of patients with cold agglutinin disease, when exposed to cold temperatures, behaves in ways that are quite different from the blood of healthy people. In affected individuals, certain proteins that normally attack bacteria (IgM antibodies), attach themselves to red blood cells and bind them together into clumps (agglutination). The antibodies activate other components of the blood, eventually causing red blood cells to be prematurely destroyed (hemolysis), thus causing anemia.[1]

Subsequent signs and symptoms can include weakness, dizziness, fatigue, headache, ringing in the ears (tinnitus), and spots before the eyes. Additional symptoms \may include irritability, bizarre behavior, absence of menstrual cycles in affected females (amenorrhea), gastrointestinal complaints, low levels of circulating red blood cells (anemia), enlargement of the spleen (splenomegaly), and/or persistent yellowing of the skin, mucous membranes, and whites of the eyes (jaundice). In some cases, affected individuals may experience sweating and coldness of the fingers and/or toes, and uneven bluish or reddish discoloration of the skin of the fingers, toes, ankles, and wrists (called acrocyanosis or Raynaud's sign). Heart failure or shock may result in some cases.[1]

Cold agglutinin disease can be divided into primary or secondary forms. The signs and symptoms vary depending on type; but in general, symptoms are associated with the destruction of red blood cells, resulting in anemia. The primary form tends to be chronic and occur in older adults, ages 50 to 60. It can cause acrocyanosis or Raynaud's sign. Secondary forms tend to be acute, and resolve much more quickly. This form usually occurs in association with an underlying disorder such as infectious diseases, immunoproliferative diseases, or other autoimmune conditions.[2][3]
Last updated: 1/23/2012

  1. Cold antibody hemolytic anemia. National Organization for Rare Disorders (NORD). 2006; Accessed 1/20/2012.
  2. Harper JL. Pediatric Cold agglutinin disease. eMedicine. August 2011; Accessed 1/20/2012.
  3. Georgy S. Cold agglutinin disease. eMedicine. November 2010; Accessed 1/20/2012.