Type of test Blood
Normal findings
 No agglutination in titers ≤ 1:64
Test explanation and related physiology
Cold agglutinins are antibodies (usually IgM) to erythrocytes. All individuals have circulating antibodies directed against RBCs, but their concentrations are often too low to trigger disease (titers < 1:64). In individuals with cold agglutinin disease, these antibodies are in much higher concentrations. At body temperatures of 28° C to 31° C, such as those encountered during winter months, these antibodies can cause a variety of symptoms, from chronic anemia because of intravascular hemolysis or extravascular sequestration of affected RBCs to acrocyanosis of the ears, fingers, or toes because of local blood stasis in the skin capillaries.
There are two forms of cold agglutinin disease: primary and secondary. The primary form has no precipitating cause. Secondary cold agglutinin disease is a result of an underlying condition, notably Mycoplasma pneumoniae. Other possible under lying conditions include influenza, mononucleosis, rheumatoid arthritis, lymphomas, HIV, Epstein–Barr virus, and cytomegalo virus. Temperature regulation is important for the performance of these tests. Under no circumstance should the cold agglutinin specimen be refrigerated.
The cold agglutinin screen is performed on all specimens first to identify most of those with titer values in the normal range. If the result is negative, no titration is required. If the result is positive, a titer with serial saline dilutions is performed.
Interfering factors
Some antibiotics (penicillin and cephalosporins) can interfere with the development of cold agglutinins.
Procedure and patient care
• See inside front cover for Routine Blood Testing.
 • Fasting: no
• Blood tube commonly used: red
Abnormal findings
Increased levels
- Mycoplasma pneumoniae infection
- Viral illness
- Infectious mononucleosis
- Multiple myeloma
- Scleroderma
- Cirrhosis
- Staphylococcemia
- Thymic tumor
- Influenza
-Rheumatoid arthritis
- Lymphoma
- Systemic lupus erythematosus
- Primary cold agglutinin disease