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Febrile/cold agglutinins

Cold agglutinins; Weil-Felix reaction; Widal test; Warm agglutinins; Agglutinins

Agglutinins are antibodies that cause the red blood cells to clump together.

• Cold agglutinins are active at cold temperatures.
• Febrile (warm) agglutinins are active at normal body temperatures.

This article describes the blood test that is used to measure the level of these antibodies in the blood.

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How the Test is Performed

A blood sample is needed.

How to Prepare for the Test

There is no special preparation.

How the Test will Feel

When the needle is inserted to draw blood, some people feel moderate pain. Others feel only a prick or stinging. Afterward, there may be some throbbing where the needle was inserted.

Why the Test is Performed

This test is done to diagnose certain infections and find the cause of hemolytic anemia (a type of anemia that occurs when red blood cells are destroyed). Knowing whether there are warm or cold agglutinins can help explain why the hemolytic anemia is occurring and direct treatment.

Normal Results

Normal results are:

• Warm agglutinins: no agglutination in titers at or below 1:80
• Cold agglutinins: no agglutination in titers at or below 1:16

The examples above are common measurements for results of these tests. Normal value ranges may vary slightly among different laboratories. Some labs use different measurements or test different samples. Talk to your doctor about the meaning of your specific test results.

What Abnormal Results Mean

An abnormal (positive) result means there were agglutinins in your blood sample.

Warm agglutinins may occur with:

• Infections, including brucellosis, rickettsial disease, salmonella infection, and tularemia
• Inflammatory bowel disease
• Lymphoma
• Systemic lupus erythematosus
• Use of certain medicines, including methyldopa, penicillin, and quinidine

Cold agglutinins may occur with:

• Infections, such as infectious mononucleosis and mycoplasma pneumonia
• Chicken pox (varicella)
• Cytomegalovirus infection
• Cancer, including lymphoma and multiple myeloma
• Listeria monocytogenes
• Systemic lupus erythematosus
• Waldenström macroglobulinemia

Risks

Risks are slight but may include:

• Excessive bleeding
• Fainting or feeling lightheaded
• Hematoma (blood accumulating under the skin)
• Infection (a slight risk any time the skin is broken)

Considerations

If a disease linked to cold agglutinin is suspected, the person needs to be kept warm.

Related Information

References

Baum SG, Goldman DL. Mycoplasma infections. In: Goldman L, Schafer AI, eds. Goldman-Cecil Medicine. 26th ed. Philadelphia, PA: Elsevier; 2020:chap 301.

Elghetany MT, Banki K. Erythrocytic disorders. In: McPherson RA, Pincus MR, eds. Henry's Clinical Diagnosis and Management by Laboratory Methods. 24th ed. Philadelphia, PA: Elsevier; 2022:chap 33.

Michel M, Jäger U. Autoimmune hemolytic anemia. In: Hoffman R, Benz EJ, Silberstein LE, et al, eds. Hematology: Basic Principles and Practice. 7th ed. Philadelphia, PA: Elsevier; 2018:chap 46.

Quanquin NM, Cherry JD. Mycoplasma and ureaplasma infections. In: Cherry JD, Harrison GJ, Kaplan SL, Steinbach WJ, Hotez PJ, eds. Feigin and Cherry's Textbook of Pediatric Infectious Diseases. 8th ed. Philadelphia, PA: Elsevier; 2019:chap 196.

Review Date: 5/4/2022  

Reviewed By: Michael M. Phillips, MD, Emeritus Professor of Medicine, The George Washington University School of Medicine, Washington, DC. Also reviewed by David C. Dugdale, MD, Medical Director, Brenda Conaway, Editorial Director, and the A.D.A.M. Editorial team.

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