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Cold Agglutinin Disease Causes, Symptoms, Signs, and Treatment

What should you know about cold agglutinin disease?

Illustration of red blood cells.

Cold agglutinin hemolytic anemia symptoms and signs include fatigue, cold hands, and leg pain.

What is cold agglutinin disease?

Cold agglutinin disease is a rare form of acquired autoimmune hemolytic anemia in which exposure to cold temperatures can trigger the body's immune system to mistakenly attack and destroy its own red blood cells.

What are the signs and symptoms of cold agglutinin disease?

Symptoms of cold agglutinin disease (CAD) can be triggered or worsened by cold temperatures or viral infections and most people with cold agglutinin disease have symptoms of hemolytic anemia such as fatigue, dizziness, headaches, cold hands and feet, pale skin, dark urine, yellowing skin and eyes (jaundice), chest pain, back pain, leg pain, vomiting, diarrhea, and heart problems.

Other symptoms of cold agglutinin disease include pain and bluish coloring of the hands and feet and mottled discoloration of the skin.

What Are the Signs and Symptoms of Anemia?

Anemia is the condition of having less than the normal number of red blood cells or less than the normal quantity of hemoglobin in the blood. The oxygen-carrying capacity of the blood is, as a result, decreased. People with anemia may experience the following symptoms and signs:

  • eel tired or lightheaded (sometimes with fainting)
  • Weakness
  • Fatigue easily
  • Have decreased energy
  • Appear pale
  • Develop palpitations or rapid heart rate
  • Experience shortness of breath

Click for more about anemia symptoms and signs »

What causes cold agglutinin disease?

Cold agglutinin disease is classified as primary (unknown cause) or secondary (caused by an underlying condition).

Is cold agglutinin disease inherited (genetic)?

Cold agglutinin disease is not a genetic illness. There is either an unknown cause (primary cold agglutinin disease) or it is caused by another condition called secondary cold agglutinin disease.

Who has cold agglutinin disease?

Middle-aged and older adults are most commonly affected with cold agglutinin disease. The illness may be just slightly more common in women than in men. Certain illnesses such as infectious mononucleosis, lymphoproliferative diseases, or mycoplasma pneumonia can make people more susceptible to developing cold agglutinin disease.

What procedures and tests diagnose cold agglutinin disease?

Cold agglutinin disease is often diagnosed based on evidence of hemolytic anemia (from symptoms and/or blood tests). Other tests to detect cold agglutinin disease include complete blood count (CBC) to detect abnormal clumping (agglutination) of red blood cells, a physical examination for spleen or liver enlargement, and antiglobulin test (Coombs test) to detect the presence of a specific type of antibody (immunoglobulin M, or IgM).

How do you treat cold agglutinin disease?

Treatment for cold agglutinin disease depends on the underlying cause, the symptoms present in an individual, and the severity of the illness. In primary cold agglutinin disease, or in patients with minimal symptoms or mild anemia, treatment often consists of measures to avoid getting cold. In secondary cold agglutinin disease that results from another medical condition, it is important to treat the underlying condition.

In severe cases of hemolysis (destruction of red blood cells), medical treatment may be needed. Medical treatments for cold agglutinin disease include rituximab (Rituxan), a drug that is an antibody that selectively reduces specific types of immune cells). The effects of treatment with rituximab can last up to 2 years.
Combined treatment with rituximab (Rituxan) and fludarabine (Fludara) may be used but there may be more side effects.
Plasmapheresis involves filtering blood to remove antibodies, but its effect is short term. It may be effective in acute hemolytic crisis and before surgery requiring hypothermia.

Use of corticosteroids and removal of the spleen have not been shown to be effective treatments for cold agglutinin disease.

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Is cold agglutinin disease cancer?

Cold agglutinin disease is not a form of cancer.

Can cold agglutinin disease be cured?

In cases of secondary cold agglutinin disease caused by bacterial or viral infections, the symptoms typically go away on their own within 6 months after the bacterial or viral infection has resolved.

What is the prognosis and life expectancy for cold agglutinin disease?

The prognosis for people with cold agglutinin disease varies based on the severity of the illness, the signs and symptoms, and any underlying cause. The outlook for people with secondary cold agglutinin disease caused by bacterial or viral infections is excellent prognosis and cold agglutinin disease symptoms usually go away within 6 months after the infection has resolved. Mild to moderate primary (unknown cause) cold agglutinin disease may also have a good prognosis if cold exposure is avoided.

People who have cold agglutinin disease caused by certain types of cancer or HIV infection generally have a poorer prognosis and possibly a shorter life expectancy due to their underlying condition.

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