About cold agglutinin disease

What is cold agglutinin disease?

Cold antibody hemolytic anemia (CAHA) is a rare autoimmune disorder characterized by the premature destruction of red blood cells (rbcs) by the body's natural defenses against invading organisms (antibodies). Normally, the red blood cells have a life span of approximately 120 days before they are destroyed by the spleen. In individuals with CAHA, the red blood cells are destroyed prematurely and the rate of production of new cells in the bone marrow can no longer compensate for their loss. The severity of the anemia is determined by the length of time that the red blood cells survive and by the rate at which the bone marrow continues to create new red blood cell production.

The immune hemolytic anemias are classified according to the optimal temperature at which the antibodies act to destroy red blood cells. As their names imply, cold antibody hemolytic anemia occurs at temperatures of approximately 0 to 10 degrees centigrade, while warm antibody hemolytic anemia (WAHA) occurs at temperatures of 37 degrees centigrade or higher.

In most cases, CAHA is a primary disorder that typically becomes apparent at 50 to 60 years of age. Symptoms and findings associated with the disorder may include fatigue; low levels of circulating red blood cells (anemia); persistent yellowing of the skin, mucous membranes, and whites of the eyes (jaundice); and/or sweating and coldness of the fingers and/or toes (digits) and uneven bluish or reddish discoloration of the skin of the digits, ankles, and wrists (acrocyanosis or Raynauds sign).

Cold antibody hemolytic anemia may also occur as a secondary disorder in association with a number of different underlying disorders such as certain infectious diseases (e.g., mycoplasma infection, mumps, cytomegalovirus, infectious mononucleosis), immunoproliferative diseases (e.g., non-Hodgkin's lymphoma, chronic lymphocytic leukemia), or connective tissue disorders (e.g., systemic lupus erythematosus). Although CAHA is known to be an autoimmune disorder, its exact underlying cause is not fully understood.

What are the symptoms for 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 causes for cold agglutinin disease?

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

What are the treatments for 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.

What are the risk factors for 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.

Is there a cure/medications 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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