Please Remove Adblock
Adverts are the main source of Revenue for DoveMed. Please remove adblock to help us create the best medical content found on the Internet.

Cold Agglutinins Blood Test

Last updated Jan. 21, 2019

Approved by: Maulik P. Purohit MD, MPH

The Cold Agglutinins Blood Test helps determine the levels of cold agglutinins in blood. It is used to diagnose hemolytic anemia.

What are other Names for this Test? (Equivalent Terms)

  • Agglutinins Blood Test
  • Cold Autoantibodies Blood Test
  • Cold-Reacting Antibodies Blood Test

What is Cold Agglutinins Blood Test? (Background Information)

  • Cold agglutinins are autoantibodies that target and destroy red blood cells during low-temperature conditions. This causes anemias and other disorders
  • Antibodies are defense proteins of the immune system that rid the body of invaders, including bacteria and viruses. An antibody recognizes its target by binding to a specific marker on its surface (known as an antigen)
  • After an antibody has bound to its antigen, the foreign invader is deactivated and prevented from causing harm. It is also marked for destruction by other cells of the immune system. 
  • Autoantibodies are abnormal antibodies that target the body’s own cells instead of foreign invaders. This results in the destruction of native cells and excessive stimulation of the immune system, which gives rise to autoimmune disease
  • Cold agglutinins are autoantibodies that react with red blood cells when exposed to cold temperatures. This leads to a decrease in red blood cell numbers due to destruction of red blood cells, which is called hemolytic anemia
  • Red blood cells are the body’s vehicles for transporting oxygen and carbon dioxide, as well as regulating blood basicity and acidity. Because of these important roles, anemias cause a variety of adverse health conditions
  • The Cold Agglutinins Blood Test helps determine the levels of cold agglutinins in blood. It is used to diagnose hemolytic anemia
  • The test is performed by making dilutions of a blood sample - for example, 2-fold, 4-fold, 8-fold, and so on - and mixing each diluted sample with red blood cells at a temperature lower than body temperature (30°C). The highest dilution in which a reaction takes place is called the titer

What are the Clinical Indications for performing the Cold Agglutinins Blood Test?

Following are the clinical indications for performing the Cold Agglutinins Blood Test:

  • Positive result from a RBC antibody screen
  • Fatigue
  • Pale skin
  • Shortness of breath
  • Headaches
  • Dizziness
  • Blueness and pain in extremities, especially when exposed to cold temperatures

How is the Specimen Collected for Cold Agglutinins Blood Test?

Following is the specimen collection process for Cold Agglutinins Blood Test:

Sample required: Blood

Process of obtaining blood sample in adults:

  • A band is wrapped around the arm, 3-4 inches above the collection site (superficial vein that lies within the elbow pit)
  • The site is cleaned with 70% alcohol in an outward spiral, away from the zone of needle insertion
  • The needle cap is removed and is held in line with the vein, pulling the skin tight
  • With a small and quick thrust, the vein is penetrated using the needle
  • The required amount of blood sample is collected by pulling the plunger of the syringe out slowly
  • The wrap band is removed, gauze is placed on the collection site, and the needle is removed
  • The blood is immediately transferred into the blood container, which has the appropriate preservative/clot activator/anti-coagulant
  • The syringe and the needle are disposed into the appropriate “sharp container” for safe and hygienic disposal

Preparation required: No special preparation is needed prior to the test.

What is the Significance of the Cold Agglutinins Blood Test Result?

A positive value for the Cold Agglutinins Blood Test is associated with a reaction taking place with a blood sample that has been diluted more than 32 times (i.e. a titer above 1:32). This may indicate: 

  • M. pneumoniae infection
  • Infectious mononucleosis, or mono
  • Cancer
  • Malaria
  • Lymphoma
  • Leukemia
  • Multiple myeloma
  • Legionnaires disease
  • Syphilis
  • HIV
  • Hepatitis C

The laboratory test results are NOT to be interpreted as results of a "stand-alone" test. The test results have to be interpreted after correlating with suitable clinical findings and additional supplemental tests/information. Your healthcare providers will explain the meaning of your tests results, based on the overall clinical scenario.

Additional and Relevant Useful Information:

  • Cold agglutinin disease is often caused by genetic defects that give rise to autoantibodies that target red blood cells in cold temperatures. However, it may also be caused by other disorders such as infections and cancer
  • The Cold Agglutinins Blood Test is not used to diagnose the disorders that may lead to cold agglutinins disease, as the test is only specific for the presence of large numbers of cold agglutinins, and not for possible underlying conditions

Certain medications that you may be currently taking may influence the outcome of the test. Hence, it is important to inform your healthcare provider of the complete list of medications (including any herbal supplements) you are currently taking. This will help the healthcare provider interpret your test results more accurately and avoid unnecessary chances of a misdiagnosis.

The following DoveMed website link is a useful resource for additional information: 


Please visit our Laboratory Procedures Center for more physician-approved health information:


References and Information Sources used for the Article:

Reviewed and Approved by a member of the DoveMed Editorial Board
First uploaded: Jan. 14, 2016
Last updated: Jan. 21, 2019