Cold Agglutinins

Test Overview

A cold agglutinins blood test is done to check for conditions that cause the body to make certain types of antibodies called cold agglutinins. Cold agglutinins are normally made by the immune system in response to infection. They cause red blood cells to clump together (agglutinate) at low temperatures. See a picture of the immune system.

Healthy people generally have low levels of cold agglutinins in their blood. But lymphoma or some infections, such as mycoplasma pneumonia, can cause the level of cold agglutinins to rise.

Higher-than-normal levels of cold agglutinins generally do not cause serious problems. Sometimes high levels of cold agglutinins can cause blood to clump in blood vessels under the skin when the skin is exposed to the cold. This causes pale skin and numbness in the hands and feet. The symptoms go away when the skin warms up. In some cases, the clumped blood cells can stop the flow of blood to the tips of the fingers, toes, ears, or nose. This is like frostbite and can cause tissue damage. In rare cases, it can cause gangrene.

Sometimes high levels of cold agglutinins can destroy red blood cells throughout the body. This condition is called autoimmune hemolytic anemia.

Why It Is Done

The cold agglutinins test may be done to:

  • See whether high cold agglutinin levels are causing autoimmune hemolytic anemia.
  • Find pneumonia caused by mycoplasma. Over half of people with pneumonia caused by mycoplasma develop an increase in cold agglutinin levels in their blood within a week of being infected. Newer tests for mycoplasma pneumonia have replaced the cold agglutinins blood test.

How To Prepare

You do not need to do anything before you have this test.

How It Is Done

The doctor drawing blood will:

  • Wrap an elastic band around your upper arm to stop the flow of blood. This makes the veins below the band larger so it is easier to put a needle into the vein.
  • Clean the needle site with alcohol.
  • Put the needle into the vein. If the needle is not placed correctly or if the vein collapses, more than one needle stick may be needed.
  • Hook a tube to the needle to fill it with blood.
  • Remove the band from your arm when enough blood is collected.
  • Put a gauze pad or cotton ball over the needle site as the needle is removed.
  • Put pressure to the site and then a bandage.

How It Feels

The blood sample is taken from a vein in your arm. An elastic band is wrapped around your upper arm. It may feel tight. You may feel nothing at all from the needle, or you may feel a quick sting or pinch.

Risks

There is very little chance of a problem from having blood sample taken from a vein.

  • You may get a small bruise at the site. You can lower the chance of bruising by keeping pressure on the site for several minutes.
  • In rare cases, the vein may become swollen after the blood sample is taken. This problem is called phlebitis. A warm compress can be used several times a day to treat this.
  • Ongoing bleeding can be a problem for people with bleeding disorders. Aspirin, warfarin (Coumadin), and other blood-thinning medicines can make bleeding more likely. If you have bleeding or clotting problems, or if you take blood-thinning medicine, tell your doctor before your blood sample is taken.

Results

A cold agglutinins blood test is done to check for conditions that cause the body to make certain antibodies called cold agglutinins. The results of the cold agglutinins test is usually reported in titers.

A titer is a measure of how much the blood sample can be diluted before the cold agglutinins can no longer be found. A titer of 1 to 8 (1:8) means that cold agglutinins can be found when 1 part of the blood sample is diluted by up to 8 parts of a salt solution (saline). A larger second number means there are more cold agglutinins in the blood. A titer of 1 to 128 means more cold agglutinins in the blood than a titer of 1 to 32.

Normal

Normal values may vary from lab to lab.

Cold agglutinins
Normal titer

Below 1 to 40 (1:40)

High values

  • High titers of cold agglutinins may be caused by infections, such as pneumonia caused by mycoplasma, infectious mononucleosis, malaria, cytomegalovirus, or other viral infections. High titers can also mean hepatitis C, cirrhosis, or autoimmune disease.
  • High levels of cold agglutinins can also be caused by diseases such as hemolytic anemia, multiple myeloma, rheumatoid arthritis, or scleroderma.
  • Very high titers of cold agglutinins (more than 1 to 1,000) can mean lymphoma is present.
  • High titers of cold agglutinins can cause symptoms when a person is exposed to cold temperatures. These symptoms can include numbness, burning, pain, or pale skin of the fingertips, toes, ears, or nose. Very high titers can mean you have a higher chance of developing blood clots (thromboses) when exposed to cold temperatures.

What Affects the Test

Reasons you may not be able to have the test or why the results may not be helpful include:

What To Think About

  • More than half of people infected with pneumonia caused by mycoplasma develop high levels of cold agglutinins. Newer tests for mycoplasma pneumonia have replaced the cold agglutinins blood test.
  • If clumped red blood cells (called a Rouleaux formation) are seen on a complete blood count (CBC) test, your doctor may order a cold agglutinins test to see whether high cold agglutinin levels are present.
  • A blood type test is done before a blood transfusion or organ transplant to make sure that the donor's and recipient's blood types match. Blood that has high levels of cold agglutinins may be hard to type. For more information, see the medical test Blood Type Test.
  • If a person has high levels of cold agglutinins and has symptoms brought on by cold temperatures, it is important for this person to be kept warm. High levels of cold agglutinins in this case could lead to frostbite, anemia, or Raynaud's phenomenon. Medicines to help lower high levels of cold agglutinins may be given when severe symptoms are brought on by cold exposure.
  • Older adults may have high titers of cold agglutinins that last for years.
  • Cold agglutinins in the blood can cause problems with automated machines that measure blood count.

References

Other Works Consulted

  • Chernecky CC, Berger BJ, eds. (2004). Laboratory Tests and Diagnostic Procedures, 4th ed. Philadelphia: Saunders.
  • Fischbach FT, Dunning MB III, eds. (2004). Manual of Laboratory and Diagnostic Tests, 7th ed. Philadelphia: Lippincott Williams and Wilkins.
  • Pagana KD, Pagana TJ (2006). Mosby’s Manual of Diagnostic and Laboratory Tests, 3rd ed. St. Louis: Mosby.

Credits

Author Maria G. Essig, MS, ELS
Editor Susan Van Houten, RN, BSN, MBA
Associate Editor Tracy Landauer
Primary Medical Reviewer Anne C. Poinier, MD - Internal Medicine
Specialist Medical Reviewer W. David Colby IV, MSc, MD, FRCPC - Infectious Disease
Last Updated June 12, 2008

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