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.
The blood of patients with cold antibody hemolytic anemia, when exposed to cold temperatures, behaves in ways that are quite different from the blood of healthy people. In those affected, for reasons and in ways that are not well understood, 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 constituents of the blood (complement) causing changes in the red cell surface membrane that results in the breakdown of the outer membrane of the red blood cell and its removal from the circulation by macrophages.
Individuals with CAHA may experience weakness, dizziness, fatigue, headache, ringing in the ears (tinnitus), and spots before the eyes. Additional symptoms and findings 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, mucuous membranes, and whites of the eyes (jaundice). In some cases, affected individuals may experience 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 Raynaud’s sign). Heart failure or shock may result in some cases.
Although cold antibody hemolytic anemia is known to be an autoimmune disorder, neither its exact underlying cause nor the process by which the disorder becomes apparent is fully understood. Autoimmune disorders occur when the body’s natural defenses (antibodies, lymphocytes, etc.) against invading organisms suddenly begin to attack perfectly healthy tissue for unknown reasons.
Cold antibody hemolytic anemia most commonly affects older people. The incidence of CAHA in the general population is about 1 in 80,000. There appears to be a slight bias in favor of females in the incidence of CAHA, with a male to female ratio of 2 to 3. Those individuals with infectious mononucleosis, lymphoproliferative diseases, or mycoplasma pneumonia are more susceptible to this disorder.
In order to differentiate hemolytic anemia from the other anemias, doctors examine the patient's blood to determine the proportion of immature red blood cells, since the number of young cells is increased in hemolytic anemia. The patient is also examined to check for spleen or liver enlargement. An antiglobulin test (Coomb's reaction) may be performed as the initial screening exam to detect the presence of immunoglobulin or complement on the red-cell membrane and to determine the specific class of immunoglobulin or complement present. In the case of cold antibody hemolytic anemia, the Coomb's test is almost always positive for immunoglobulin M (IgM).
If symptoms are mild or if destruction of red blood cells seems to be slowing of its own accord, usually no treatment is needed. If, however, 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. Patients on steroid drugs must be carefully monitored while the drug is being used.
When people do not respond to corticosteroids or when the corticosteroid causes intolerable side effects, surgery to remove the spleen (splenectomy) may be the next treatment.
When 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.
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 in which blood transfusions are necessary, certain guidelines must be followed because of the temperature sensitivities involved.
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