Febrile/Cold Agglutinins

Written by Dale Kiefer | Published on July 5, 2012
Medically Reviewed by George Krucik, MD

Febrile/Cold Agglutinins

Febrile (warm) and cold agglutinins are antibodies. Antibodies are proteins produced by the immune system to combat infection. They cause red blood cells to clump together (agglutinate). When this happens in the bloodstream, red blood cells cannot perform normally.

Febrile and cold agglutinins are autoantibodies. Autoantibodies are antibodies that attack part of the body, instead of an illness or disease. Febrile and cold agglutinins is also the name of a blood test that tests for the presence of these antibodies.

Sometimes, the febrile agglutinins test is called the fever evaluation test.

What Are Agglutinins?

Both febrile and cold agglutinins are linked to a variety of illnesses and diseases. They can be present in the blood long after an infection or signal a disease that has not yet shown any symptoms.

Why is This Test Needed?

The febrile/cold agglutinins test is performed to diagnose a number of diseases and infections. By testing for the presence of these antibodies in the blood, your doctor can determine what is wrong and then recommend appropriate treatment.

Patients may have cold agglutinins circulating in the bloodstream for years with no ill effects. However, if the patient should need a blood transfusion, cold agglutinins may trigger a fatal reaction. They can also complicate open-heart surgery or other surgeries in which blood is diverted from the heart.

Ordinarily, blood is diverted from the circulation and chilled during these types of surgeries (hypothermic cardiopulmonary bypass). However, chilling the blood in patients with cold agglutinins causes the agglutinins to attack the patient’s red blood cells.

Hemolytic Anemia

One of the most common uses of the febrile/cold agglutinins test is to diagnose hemolytic anemia. In this condition, red blood cells break down too soon or too often. Ordinarily, a healthy red blood cell lasts for about four months.

Patients with anemia may experience symptoms ranging from lightheadedness to irritability and loss of concentration. Anemia may also cause headaches.

Other Infections Linked to Cold Agglutinins

Cold agglutinins may also be present in the blood after infection with mononucleosis or HIV, especially among children. Among adults, their presence can indicate diseases such as lymphoma or chronic lymphoid leukemia, which are types of cancer that affect white blood cells.

Several infectious diseases are linked to febrile agglutinins. These include:

  • brucellosis (an infectious disease spread from animals to humans)
  • salmonella
  • rickettsial diseases like typhus fever and spotted fever
  • tularemia (an infectious disease spread by animals to humans)

Lymphoma and leukemia may also be associated with febrile agglutinins. However, as there are more specific tests for these diseases, the febrile agglutinins test is seldom used to diagnose these types of cancer.

The Test

Febrile/cold agglutinins is a diagnostic blood test. Your doctor will tie a band around your upper arm to help blood fill your veins. A small needle will be inserted in the vein and blood will be collected in a glass tube. This is relatively quick and painless. Your doctor will then send the blood to a lab, where technicians will observe how the blood reacts to being chilled or heated.


The results will be reported as either positive or negative for cold or febrile agglutinins. A medical professional will interpret the results. If the test is positive, your doctor will recommend treatment or further testing depending on the underlying cause of the agglutinins.

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