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Cold agglutinin disease


Other Names for this Disease

  • Anemia, hemolytic, cold antibody
  • CAD
  • Cold antibody disease
  • Cold antibody hemolytic anemia
See Disclaimer regarding information on this site. Some links on this page may take you to organizations outside of the National Institutes of Health.

Overview

What is cold agglutinin disease?

What are the signs and symptoms of cold agglutinin disease?

What causes cold agglutinin disease?

Is cold agglutinin disease inherited?

How is cold agglutinin disease diagnosed?

How might cold agglutinin disease be treated?

What is cold agglutinin disease?

Cold agglutinin disease (CAD) is a rare form of autoimmune hemolytic anemia. In this condition, the immune system makes antibodies that attack the body's own red blood cells. This causes the blood cells to die prematurely (hemolysis).[1][2] Symptoms may include pallor and fatigue; back and leg pain; headache; vomiting; diarrhea; and dark urine. CAD gets its name from the fact that the antibodies react at temperatures below 37ºC, so a cold environment may trigger the condition or make it worse. It can be primary (idiopathic) or secondary, due to an underlying condition such as an infection, another autoimmune disease, or certain cancers.[1][2] Treatment often involves avoidance of cold temperatures.[3]
Last updated: 3/11/2014

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.[4]

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.[4]

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.[1][2]
Last updated: 1/23/2012

What causes cold agglutinin disease?

The exact underlying cause of cold agglutinin disease (CAD) is not fully understood. The underlying cause of the primary form is often unknown (idiopathic). Secondary CAD may be associated with infections (such as mycoplasma, Epstein-Barr virus, cytomegalovirus, mumps, varicella, rubella, adenovirus, HIV, influenza, hepatitis C, legionnare disease, syphilis, or listeriosi); other autoimmune diseases (such as systemic lupus erythematosus); or certain cancers (such as non-Hodgkin's lymphoma or chronic lymphocytic leukemia).[1][2][4]
Last updated: 5/15/2014

Is cold agglutinin disease inherited?

Cold agglutinin disease (CAD) is not an inherited condition and does not run in families. It is designated as either idiopathic or primary (not associated with an underlying condition), or secondary (associated with or caused by another condition). In some cases CAD may be multifactorial, which means that multiple environmental factors and multiple genes may interact to predispose a person to developing CAD.[5] However, to our knowledge, no disease-causing genes have been identified and no familial cases have been reported.
Last updated: 5/15/2014

How is cold agglutinin disease diagnosed?

A diagnosis of cold agglutinin disease (CAD) may be made after several types of tests are performed by a health care provider. In some cases, the diagnosis is first suspected by chance, from a standard complete blood count (CBC) that detects abnormal clumping (agglutination) of the red blood cells. In most cases, the diagnosis is based on evidence of hemolytic anemia (from symptoms and/or blood tests). A person may also be physically examined for spleen or liver enlargement. An antiglobulin test (called the Coombs test) may be performed to determine the presence of a specific class of immunoglobulin or complement.  In people with CAD, the Coomb's test is almost always positive for immunoglobulin M (IgM).[6]

Detailed information about the various tests used to make a diagnosis of CAD is available on Medscape Reference's Web site.
Last updated: 3/11/2014

How might cold agglutinin disease be treated?

If symptoms are mild or if the destruction of red blood cells seems to be slowing of its own, usually no treatment is needed. However, if the rate at which red blood cells are being destroyed appears to be increasing, a corticosteroid drug such as prednisone is usually the first choice for treatment. High doses may be used at first, followed by a gradual tapering of the dose over many weeks or months. Those on steroid drugs must be carefully monitored while the drug is being used because overuse can lead to dependence and severe side effects.[4]

When people do not respond to corticosteroids or when the corticosteroid causes intolerable side effects, surgery to remove the spleen (splenectomy) may be considered. If the destruction of red blood cells persists after removal of the spleen or when surgery cannot be performed, immunosuppressive drugs, such as cyclophosphamide or azathioprine, may be prescribed.[4]

Plasmapheresis, which involves filtering blood to remove antibodies, is occasionally helpful when other treatments fail. When red blood cell destruction is severe, blood transfusions are sometimes needed, but they do not treat the cause of the anemia and provide only temporary relief. In cases where blood transfusions are necessary, certain guidelines must be followed because of the temperature sensitivities involved.[4]
Last updated: 12/15/2011

References
  1. Harper JL. Pediatric Cold agglutinin disease. eMedicine. August 2011; http://emedicine.medscape.com/article/954954-overview. Accessed 1/20/2012.
  2. Georgy S. Cold agglutinin disease. eMedicine. November 2010; http://emedicine.medscape.com/article/135327-overview. Accessed 1/20/2012.
  3. Marc Michel. Cold agglutinin disease. Orphanet. August, 2010; http://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=56425. Accessed 3/11/2014.
  4. Cold antibody hemolytic anemia. National Organization for Rare Disorders (NORD). 2006; http://www.rarediseases.org/rare-disease-information/rare-diseases/byID/723/viewAbstract. Accessed 1/20/2012.
  5. Marc Michel. Cold agglutinin disease. Orphanet. August, 2010; http://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=56425. Accessed 5/15/2014.
  6. Anemia, Hemolytic, Cold Antibody. NORD. March 27, 2008; http://www.rarediseases.org/rare-disease-information/rare-diseases/byID/723/viewAbstract. Accessed 3/11/2014.


Other Names for this Disease
  • Anemia, hemolytic, cold antibody
  • CAD
  • Cold antibody disease
  • Cold antibody hemolytic anemia
See Disclaimer regarding information on this site. Some links on this page may take you to organizations outside of the National Institutes of Health.