Also Known As
Agglutinins
Cold Autoantibodies
Cold-Reacting Antibodies
Formal Name
Cold Agglutinins
This article was last reviewed on
This article waslast modified on
May 27, 2018.
At a Glance
Why Get Tested?

To help determine the cause of hemolytic anemia; to help diagnose cold agglutinin disease

When To Get Tested?

When you have symptoms associated with anemia and/or pain, paleness, and bluing in the fingers, toes and tips of the ears that occurs after exposure to cold temperatures; when you have been diagnosed with hemolytic anemia and your health practitioner is investigating the cause

Sample Required?

A blood sample drawn from a vein in your arm

Test Preparation Needed?

None

You may be able to find your test results on your laboratory's website or patient portal. However, you are currently at Lab Tests Online. You may have been directed here by your lab's website in order to provide you with background information about the test(s) you had performed. You will need to return to your lab's website or portal, or contact your healthcare practitioner in order to obtain your test results.

Lab Tests Online is an award-winning patient education website offering information on laboratory tests. The content on the site, which has been reviewed by laboratory scientists and other medical professionals, provides general explanations of what results might mean for each test listed on the site, such as what a high or low value might suggest to your healthcare practitioner about your health or medical condition.

The reference ranges for your tests can be found on your laboratory report. They are typically found to the right of your results.

If you do not have your lab report, consult your healthcare provider or the laboratory that performed the test(s) to obtain the reference range.

Laboratory test results are not meaningful by themselves. Their meaning comes from comparison to reference ranges. Reference ranges are the values expected for a healthy person. They are sometimes called "normal" values. By comparing your test results with reference values, you and your healthcare provider can see if any of your test results fall outside the range of expected values. Values that are outside expected ranges can provide clues to help identify possible conditions or diseases.

While accuracy of laboratory testing has significantly evolved over the past few decades, some lab-to-lab variability can occur due to differences in testing equipment, chemical reagents, and techniques. This is a reason why so few reference ranges are provided on this site. It is important to know that you must use the range supplied by the laboratory that performed your test to evaluate whether your results are "within normal limits."

For more information, please read the article Reference Ranges and What They Mean.

What is being tested?

Cold agglutinins are autoantibodies produced by a person's immune system that mistakenly target red blood cells (RBCs). They cause RBCs to clump together when a person is exposed to cold temperatures and increase the likelihood that the affected RBCs will be destroyed by the body. This test detects and measures the amount of cold agglutinins in the blood.

When the presence of cold agglutinins in a person's blood leads to significant RBC destruction, it can cause hemolytic anemia and lead to a low RBC count and hemoglobin. This rare form of autoimmune hemolytic anemia is known as cold agglutinin disease. Cold agglutinin disease may be primary or secondary, induced by some other disease or condition.

Primary cold agglutinin disease typically affects those who are middle age to elderly, and it tends to continue over time (chronic). Secondary cold agglutinin disease may affect anyone and may be acute or chronic, temporary or persistent. It may cause hemolytic anemia to a greater or lesser degree and is associated with a variety of conditions, such as:

The cold agglutinin test is not routinely ordered. It is a test that has been available for a long time, but it has become less commonly used as more specific tests for secondary causes, such as Mycoplasma pneumoniae infection, have become available.

How is the sample collected for testing?

A blood sample is obtained by inserting a needle into a vein in the arm. The sample requires special handling and must be kept within a specific temperature range (not refrigerated) during transport to the laboratory and prior to testing.

Is any test preparation needed to ensure the quality of the sample?

No test preparation is needed.

Accordion Title
Common Questions
  • How is it used?

    A cold agglutinin test may be used to help detect cold agglutinin disease and determine the cause of a person's hemolytic anemia. It may be used as a follow-up test after a complete blood count (CBC) shows a decrease in a person's red blood cell (RBC) count and hemoglobin, especially if these findings are linked to an exposure to cold temperatures.

    Cold agglutinin disease is a rare autoimmune disorder in which autoantibodies produced by a person's immune system mistakenly target and destroy RBCs, causing hemolytic anemia. These autoantibodies are cold-reacting and can cause signs and symptoms related to anemia after an affected person is exposed to cold temperatures. This disease may be classified as either primary or secondary, triggered by an infection or other condition.

    This test is performed on a series of dilutions of a blood sample that are prepared in test tubes and then cooled to a low temperature, typically 4°C (39.2°F). Each dilution is then evaluated for clumped RBCs, with the results reported as a titer – the highest dilution that shows detectable clumping. When cold agglutinins are present, RBC clumping is visible while the sample is cold and disappears when the sample is warmed. The exact temperature at which this will occur will vary as some cold agglutinins will react over a wider temperature range than others.

  • When is it ordered?

    This test may be ordered when a person has reactions to cold temperature exposures and has signs of hemolytic anemia that may be due to cold agglutinin disease. Symptoms may include:

    • Fatigue, weakness, lack of energy, pale skin (pallor), dizziness and/or headaches from anemia
    • In some cases, painful bluish fingers, toes, ears, and the tip of the nose that occur with exposure to cold temperatures
  • What does the test result mean?

    The result of a cold agglutinin test is typically reported as a titer, such as 1:64 or 1:512. A higher number means that there are more autoantibodies present. Higher titers of autoantibodies and those that react at warmer temperatures are associated with hemolytic anemia and worse symptoms.

    The degree of red blood cell (RBC) hemolysis and hemolytic anemia will vary from person to person and with each episode of cold exposure. Some conditions, such as infectious mononucleosis, are frequently associated with elevated cold agglutinins but rarely associated with anemia.

    Sometimes a cold agglutinin test may be run at one or more additional temperatures that are lower than body temperature but warmer than 4°C, such as performed at 30°C (86°F) to determine the point at which the RBCs start to clump. This information may be important for someone who has chronically elevated cold agglutinins and is being considered for a surgery that involves body cooling.

  • Is there anything else I should know?

    A cold agglutinin test may rarely be ordered to identify increased cold agglutinins if someone has a condition that has been linked to secondary cold agglutinin disease, such as infectious mononucleosis or a Mycoplasma pneumoniae infection. Since the test is not specific for these conditions, it is not typically ordered to diagnose or monitor them.

  • If I have elevated cold agglutinins, is there anything I can do to make them go away or decrease them?

    This is something that your doctor will need to determine. Consult your health care provider on what steps can be taken to decrease cold agglutinins.

  • What can I do to avoid the symptoms of cold agglutinin disease?

    To minimize episodes of painful discolored fingers and toes, and of abnormal red blood cell destruction (hemolysis), it is important to avoid and/or limit exposure to cold temperatures. People have differing sensitivities; some may be affected by drinking or eating something cold or by taking a cold shower. You should talk to your health care provider about strategies to manage your condition.

View Sources

Vorvick, L. (Updated 2012 May 31). Febrile/cold agglutinins. MedlinePlus Medical Encyclopedia [On-line information]. Available online at http://www.nlm.nih.gov/medlineplus/ency/article/003549.htm through http://www.nlm.nih.gov. Accessed August 2013.

Aljubran, S. and Lockey, R. (MD : (Updated 2013 January 25) Cold Agglutinin Disease Medscape Reference [On-line information]. Available online at http://emedicine.medscape.com/article/135327-overview through http://emedicine.medscape.com. Accessed August 2013.

Delgado, J. and Hill, H. (Updated 2013 July). Cold Agglutinin Disease. ARUP Consult [On-line information]. Available online at http://www.arupconsult.com/Topics/ColdAgglutinin.html?client_ID=LTD through http://www.arupconsult.com. Accessed August 2013.

Schick, P. et. al. (Updated 2013 February 21) Hemolytic Anemia. Medscape Reference [On-line information]. Available online at http://emedicine.medscape.com/article/201066-overview through http://emedicine.medscape.com. Accessed August 2013.

(© 1995-2013) Cold Agglutinin Titer, Serum. Mayo Clinic Mayo Medical Laboratories [On-line information]. Available online at http://www.mayomedicallaboratories.com/test-catalog/Overview/8992 through http://www.mayomedicallaboratories.com. Accessed August 2013.

Lichtin, A. (Revised 2009 February). Autoimmune Hemolytic Anemia. Merck Manual for Healthcare Professionals [On-line information]. Available online through http://www.merckmanuals.com. Accessed August 2013.

Stone, M. (2010 October 28). Heating up cold agglutinins. Blood v 116 (17) 3119-3120. [On-line information]. Available online at http://bloodjournal.hematologylibrary.org/content/116/17/3119.full through http://bloodjournal.hematologylibrary.org. Accessed August 2013.

Waites, K. (Updated 2012 September 28). Mycoplasma Infections. Medscape Reference. [On-line information]. Available online at http://emedicine.medscape.com/article/223609-overview through http://emedicine.medscape.com. Accessed August 2013.

Pagana, K. D. & Pagana, T. J. (© 2011). Mosby's Diagnostic and Laboratory Test Reference 10th Edition: Mosby, Inc., Saint Louis, MO. Pp 279-280.

Ask a Laboratory Scientist

 

Your questions will be answered by a laboratory scientist as part of a voluntary service provided by one of our partners, the American Society for Clinical Laboratory Science (ASCLS). Click on the Contact a Scientist button below to be re-directed to the ASCLS site to complete a request form. If your question relates to this web site and not to a specific lab test, please submit it via our Contact Us page instead. Thank you.

Contact a Scientist