|
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:
-
Cold Agglutinin Disease
can be caused by an underlying infectious disease (mycoplasma pneumonia, mumps,
mononucleosis), lymphoproliferative disease (lymphoma, chronic lymphocytic
leukemia), or connective tissue disorder (lupus). This form, accounting for about
50% of CAD patients, is referred to as Secondary CAD, and tends to resolve if
there is improvement in the underlying condition.
According to Norway's Drs. Sigbjørn Berentsen, Klaus Beiske, and Geir Tjonnfjørd
in their most recent papers (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."
-
Both Primary and Secondary Cold Agglutinin
Disease are acquired conditions, not inherited. One can have “warm
agglutinins” and both warm and cold agglutinins at the same time. Warm
antibody disease is easier to treat.
-
Exposure to cold may significantly worsen anemia.
-
Many people with CAD also can be affected by two conditions called Raynaud’s
phenomenon and acrocyanosis.
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.
-
Young people can develop CAD as a result of some
other disease. It is generally self-limiting.
-
The onset of CAD can occur suddenly or gradually
and typically first appears in individuals in their 50’s, 60’s or 70’s. Some
studies suggest that it affects slightly more women than men and this may be
due to the fact that women comprise a greater proportion of the senior
population.
-
Some signs of anemia are fatigue, headache, lack
of energy and stamina, a yellow pallor and perhaps a yellowing of the eyes,
dark urine, irritability, mental confusion, and an enlarged spleen.
-
Some individuals with CAD have low levels of cold
antibodies and may not have overt symptoms while others having a very high
antibody titer and low hemoglobin, may require blood transfusions as a
temporary measure. (See
Treatment Options
Page)
-
This was forwarded by a
CADdy and its origin is unkown:
Certain disease states are marked by the appearance of antibodies capable of
agglutinating red blood cells at cold temperatures. These cold agglutinins are
usually IgM class autoantibodies which recognize specific sites on red blood
cells. They can be transiently associated with infections such as mycoplasma
pneumonia and infectious mononucleosis, or be persistently present in diseases
such as Waldenstrom’s macroglobulinemia, chronic lymphocytic leukemias, and
idiopathic cold agglutinin disease. Post-infectious cold agglutinins are
usually polyclonal, whereas cold agglutinins associated with B-cell neoplasms
are generally monoclonal. The effects of cold agglutinins can range from
minimal to severe hemolytic anemia. The degree of red blood cell destruction
depends upon complex factors, including the titer of the antibody (greatest
serum dilution able to agglutinate red cells) and the thermal amplitude
(maximum temperature at which agglutination of red cells still occurs.)
Generally, high titers occur with high thermal amplitudes. However, there are
cases in which even low titers can be clinically significant if the reactive
temperature is very high. If a cold agglutinin has a high thermal amplitude,
special measures must be taken to keep the patient’s body temperature above
the reaction temperature. In such cases, ordinary room temperature may trigger
agglutination. Blood transfusions pose special problems unless the cross
matching has been done at 37°C. and the transfused cells have been washed to
minimize the amount of complement in the transfusion.
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. |
