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Cold Agglutinins

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Also known as: Agglutinins; Cold Autoantibodies; Cold-Reacting Antibodies
Formal name: Cold Agglutinins
Related tests: Complete Blood Count, Reticulocyte Count, Mycoplasma, Mono Test, Warm Agglutinins

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?


The Test Sample

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.

NOTE: If undergoing medical tests makes you or someone you care for anxious, embarrassed, or even difficult to manage, you might consider reading one or more of the following articles: Coping with Test Pain, Discomfort, and Anxiety, Tips on Blood Testing, Tips to Help Children through Their Medical Tests, and Tips to Help the Elderly through Their Medical Tests.

Another article, Follow That Sample, provides a glimpse at the collection and processing of a blood sample and throat culture.

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

No test preparation is needed.

The Test

Common Questions

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Article Sources

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NOTE: This article is based on research that utilizes the sources cited here as well as the collective experience of the Lab Tests Online Editorial Review Board. This article is periodically reviewed by the Editorial Board and may be updated as a result of the review. Any new sources cited will be added to the list and distinguished from the original sources used.

Vorvick, L. (Updated 2012 May 31). Febrile/cold agglutinins. MedlinePlus Medical Encyclopedia [On-line information]. Available online at through Accessed August 2013.

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

Delgado, J. and Hill, H. (Updated 2013 July). Cold Agglutinin Disease. ARUP Consult [On-line information]. Available online at through Accessed August 2013.

Schick, P. et. al. (Updated 2013 February 21) Hemolytic Anemia. Medscape Reference [On-line information]. Available online at through Accessed August 2013.

(© 1995-2013) Cold Agglutinin Titer, Serum. Mayo Clinic Mayo Medical Laboratories [On-line information]. Available online at through Accessed August 2013.

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

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

Waites, K. (Updated 2012 September 28). Mycoplasma Infections. Medscape Reference. [On-line information]. Available online at through 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.