Cold Agglutinin Disease, a rare blood disorder, is a type of Autoimmune Hemolytic Anemia. Cold agglutinin antibodies are made in your bone marrow and high levels can occur when your immune system malfunctions. The body mistakenly perceives, as foreign, the very antibodies that it produces and sets up an autoimmune response thereby prematurely killing the red blood cells (hemolysis).
The antibodies called cold agglutinins, are activated by cold temperatures and react by causing a sticking together or clumping of the red blood cells to which they are attached. The temperature, at which the agglutination (clumping) takes place, varies from patient to patient. A thermal study may be done to determine the level.
PLEASE NOTE: According to Dr. Sigbjørn Berentsen et. al., the thermal amplitude, defined as the highest temperature at which the antibody will react with the antigen, appears to be more important than the titer with respect to the pathogenicity of (capacity to cause) CAD.
Cold agglutinins or cold antibodies occur naturally in nearly everyone. These natural cold auto antibodies occur at low titers, less than 1:64 measured at 4º C. and have no activity at higher temperatures. Pathologic cold agglutinins (such as with CAD) occur at titers of 1:64-100,000 and react at 28-31ºC and sometimes near or at 37ºC. Those individuals with antibodies reacting higher than 37ºC are said to have Warm Antibody Disease.
The cold agglutinin antibodies, usually of the IgM variety, (much less frequently IgG or IgA) combine with complement and attack the antigen on the surface of red blood cells causing the cells to burst open and release hemoglobin (hemolysis). When the rate of destruction exceeds the ability of the bone marrow to produce an adequate number of oxygen-carrying red cells, then anemia occurs. The greater the hemolysis, the more severe the anemia unless the body is compensating on its own or due to help from treatments such as Rituxan, Mabthera, Procrit, folic acid or others. (See Medical Terms Page)
Normal red blood cells live about 120 days and become smaller in size as they approach maturity. New young cells are larger and individuals with Cold Agglutinin Autoimmune Hemolytic Anemia have a greater number of large, younger cells than older, smaller ones. These can be measured by a CBC (complete blood count) which also tests for hemoglobin, the number of oxygenated red cells circulating in the blood, and many other blood components. The normal range for women is 12-16 and for men 14-18. In some countries the units of measurement are different and these become 120-160 and 140-180.
Additional Information about CAD:
According to Norway’s Drs. Sigbjørn Berentsen, Klaus Beiske, and Geir Tjonnfjørd in their paper (October 2007 – see Links Page), the other 50% of CAD patients are said to have Primary CAD. It is now believed that 10% of those with Primary CAD are idiopathic (no known cause) and 90% are considered to have a low grade lymphoproliferative bone marrow disorder. They find that “Except in the uncommon event of transformation, the lymphoproliferative B-cell disorders seldom, if ever, show features of a clinically overt lymphoma (3-4% of patients) even after decades.”
Raynaud’s phenomenon is triggered when cold constricts small arteries usually in the fingers and toes but can also affect other parts of the body such as the nose, ears, and face. The digits become pale or bluish and can be numb, tingle, or have a burning sensation. As re-warming takes place, the skin may be reddish then return to normal. (See Links Page)
Acrocyanosis is a painless disorder caused by constriction or spasms of small blood vessels due to cold. People with the disease tend to be uncomfortable with sometimes swollen, sweaty, cold, bluish colored fingers, hands and feet. Warming decreases the bluishness.
When one is diagnosed with Cold Agglutinins, in addition to a CBC (complete blood count), doctors customarily do a battery of tests to determine what is causing the Autoimmune Hemolytic Anemia. Often, a bone marrow biopsy is performed to rule out any underlying lymphoproliferative disease such as lymphoma or leukemia.
When you have CAD, you need to be certain that you keep warm at all times. For some, anything cold entering your body could cause an autoimmune response resulting in red cell destruction.
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