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Cold agglutinin disease


This is a disorder in which RBCs – in their own serum or in other serum – clump together (agglutinate) in response to slight cooling (below 86° F). The clumping is caused by a group of antibodies called agglutinins. Hemolysis, hemoglobinuria, and hemosiderinuria may be present.1


Cold agglutinin disease is a rare type of autoimmune hemolytic anemia in which the body’s immune system mistakenly attacks and destroys its own red blood cells. When affected people’s blood is exposed to cold temperatures (32º to 50º F), certain proteins that normally attack bacteria (IgM antibodies) attach themselves to red blood cells and bind them together into clumps (agglutination). This eventually causes red blood cells to be prematurely destroyed (hemolysis) leading to anemia and other associated signs and symptoms.2


CAD can make you feel weak and tired. Other signs of it include:3


  • Dizziness and headaches
  • Sore back, legs, or joints
  • Ringing in your ears
  • Irritability or changes in your behavior
  • Pale or yellow skin
  • Vomiting or diarrhea
  • Cold feet or hands
  • Chest pains or an irregular heartbeat


In women, cold agglutinin disease sometimes keeps them from having periods. Some people who have cold agglutinin disease also may get a cold, numb feeling and loss of color in their fingers or toes, known as Raynaud’s phenomenon. Symptoms are typically worse in the winter, when temperature are lower.3

Causes and Risk Factors

Cold agglutinin disease can be primary (unknown cause) or secondary, due to an underlying condition such as an infection, another autoimmune disease, or certain cancers.2


Cold Agglutination | CELL-DYN Ruby
Cold Agglutinin Disease | Alinity hq
1. Boston Childern’s Hospital. Red Blood Cell Disorders Symptoms & Causes.
2. Cold agglutinin disease.
3. What Is Cold Agglutinin Disease?
Image source: Fahmi Yousef Khan; Mohamed A.yassin. Mycoplasma pneumoniae associated with severe autoimmune hemolytic anemia: case report and literature review. February 2009.
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