Cold Agglutinin Disease is known by a number of other names:

  • Autoimmune Hemolytic Anemia (Anaemia)
  • Cold Agglutinin Autoimmune Hemolytic Anemia (Anaemia) (CAIHA)
  • Cold Haemagglutinin Disease (CHD)
  • Coombs Positive Hemolytic Anemia (Anaemia)
  • Primary Chronic Cold Agglutinin Disease
  • Cold Hemolytic Anemi


Occurs suddenly. Symptoms or signs that begin and worsen quickly, not chronic.


The term is used to describe the process of red blood cells clumping (agglutinating) in response to the cold-reacting antibodies which bind with antigens attached to the red cells. The blood clumping could cause the skin to appear blue on the face, legs, ears or other areas of the body.


One is considered anemic when the red blood cells are destroyed faster than the body can replenish them causing the hemoglobin level to drop below the norm of 12 for women and 14 for men. In some countries, the units of measurement are different, and 12.0 becomes 120, and 14.0 becomes 140. Red blood cells distribute the oxygen throughout the body to nourish muscles, tissues, heart, kidneys, lungs, and when there are too few red cells, one may experience loss of energy, fatigue, rapid heartbeat, shortness of breath, dizziness, mental confusion, muscle weakness, and other symptoms of anemia.


An antigen is any substance that causes your immune system to produce antibodies against it. An antigen may be a foreign substance from the environment or it may be formed within the body, as with bacterial toxins or tissue cells.

Human Antibody
An antibody, also known as an immunoglobulin, is a protein (a chain of amino acids) produced by the body’s immune system, B-cells. Antibodies react in response to antigens (Intruders), which can be viruses, bacteria or chemicals. Each antibody binds to and attacks one particular antigen. For CAD, when the abnormal B-Cell immunoglobulins, mostly of the IgM isotype, are activated by cold temperatures, they attack the antigens attached to red blood cells causing agglutination and cell death. In some cases, CAD patients are always hemolyzing.
Some antibodies are autoantibodies and attack our own tissues.
Monoclonal Antibody Drug (mAbs) Therapy
Some monoclonal antibodies (mAbs) are a type of immunotherapy such as Rituxan. mAbs are man-made proteins that act like human antibodies in the immune system.
Rituximab (Rituxan) (MabThera), eculizumab (Solaris), sutimlimab are examples of mAbs as are all other monoclonal antibody drugs whose names end in mab.


Of or relating to an immune response by the body against one of its own tissues, cell, or molecules.
Blood Count Refers to the number of red blood cells (erythrocytes), white cells (leukocytes), and platelets in a definite volume of blood. The red blood count (RBC) is expressed as the Hemoglobin.

Blood Transfusion

When it becomes necessary to quickly boost the number of red blood cells in your body, due to very low hemoglobin, a blood transfusion is administered. Washed packed red cells are infused intravenously, usually in the forearm. For those with Cold Agglutinin Disease, it is essential to use a blood warmer to prevent agglutination (clumping) of the transfused blood.

CBC Test
Complete Blood Count

Means severe/existing for a long time as in chronic indigestion.
Cold Agglutinin Disease
A rare type of autoimmune hemolytic anemia in which the body’s immune system autoantibodies mistakenly attack its own red blood cells. This causes red blood cells to be prematurely destroyed (hemolysis) leading to anemia and other associated signs and symptoms.  


Primary Cold Agglutinin Disease is a clonal B-cell low-grade Lymphoproliferative Disorder (LPD) of the bone marrow which is distinct from lymphoplasmacytic lymphoma.

If the Cold Agglutinin condition occurs as the result of some other disease, it is known as Secondary CAD. Generally, curing or arresting the underlying disease will result in resolving the CAD.   


An ancient defense mechanism that uses 30 proteins in the blood. It is named complement because the system helps antibodies kill invaders. In Cold Agglutinin Disease, complement and antibodies bind to and attack the antigen on red blood cells causing agglutination and complement activation by the classical complement pathway. The complex process leads to hemolysis and eventual anemia.


The fraction of blood which is red blood cells, normally about 45%. Normally the ratio of hematocrit Hct to hemoglobin Hgb is 3:1


Hemoglobin or haemoglobin, frequently referred to as Hb or Hgb, is a complex protein found in red blood cells that carry oxygen from the lungs to the body tissues and carbon dioxide from the tissues to the lungs. It gives blood it’s red color.

Hemoglobin is one of the most important numbers for those of us with CAD, as it indicates to what degree we are anemic. Normal values for women are approximatly12-16 and men 14-18.  There is cause for concern when values trend and remain much below the norms and the patient is symptomatic. Usually a low of about 7.0 or less will necessitate a transfusion. The most severe cases of CAD can be transfusion dependent.

In the US, hemoglobin is quoted as a value of 11.5 (example), whereas in other countries it may be written as 115.

Means the destruction/breaking open of red blood cells and the release of hemoglobin into the blood plasma. Normally, red cells live for 110-120 days before they are destroyed by the spleen and/or liver. Some diseases and processes cause premature breakdown of red blood cells, leaving an abnormally small number of red cells available for transporting oxygen. One such disease is Cold Agglutinin Disease.

Plasmapheresis (PP)
A method of removing blood plasma from the body by withdrawing blood, separating it into plasma and cells, transfusing the cells back into the bloodstream. It is performed specifically to remove antibodies in treating autoimmune conditions. PP may be used prior to a surgery or as a pretreatment before a course of Rituxan or chemotherapy. Plasmapheresis is generally only a temporary measure.


The word Titer, is used to describe the concentration of Cold Agglutinin antibodies you have in your blood. A negative titer is less than about 1:32. A person with Cold Agglutinin Disease may have a positive titer of 1:64 or greater and can go as high as 50-100,000. The titer is a measurement obtained after diluting the blood with a salt solution to determine the highest level at which the Cold Agglutinins are no longer detectable. That number is then considered your titer, also known as your antibody load. The greater the quantity of antibodies, the more likely one is affected by the disease. 


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