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This article was last reviewed on
This article waslast modified on
April 25, 2018.
At a Glance
Why Get Tested?

To determine if symptoms, like sensitivity of extremities to cold, are due to the presence of abnormal proteins called cryoglobulins in the blood, which can be associated with a variety of diseases

When To Get Tested?

When you have symptoms such as a rash, bruising, pain, weakness, joint pain, and/or paleness and coolness of the extremities that occur at cold temperatures

Sample Required?

A blood sample drawn from a vein in your arm

Test Preparation Needed?


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?

Cryoglobulins are circulating proteins, specifically immunoglobulins (i.e., IgG, IgM, IgA or light chains), that clump together (precipitate) when they are exposed to cold and dissolve when warmed. They may be present in small quantities in the blood of some healthy people but are most frequently associated with abnormal protein production and a variety of diseases and conditions. This test detects and measures the relative quantity of cryoglobulins in the blood.

Precipitated cryoglobulins can slow the flow of blood and block small blood vessels. The presence of large amounts of cryoglobulins in the blood, called cryoglobulinemia, can cause symptoms such as bruising, rashes, joint pain, weakness, and Raynaud phenomenon – pain, paleness, bluing, numbness, tingling and coldness in the fingers and toes with exposure to cold. (These symptoms can also occur in people who do not have cryoglobulinemia.) Cryoglobulins can cause tissue damage that leads to skin ulcers and, in severe cases, to gangrene. They can activate the immune system, leading to the deposit of immune complexes in tissues, and cause inflammation, bleeding, and clotting that can affect circulation in organs such as the kidneys and liver.

Cryoglobulins may be found in the blood with a variety of conditions, including infections such as Lyme disease, infectious mononucleosis (mono), hepatitis C, and HIV/AIDS, kidney disease, autoimmune diseases such as systemic lupus erythematosus, rheumatoid arthritis, and Sjögren syndrome, lymphoproliferative diseases such as multiple myeloma, lymphoma and lymphoid leukemia, and disorders associated with inflammation of blood vessels (vasculitis) such as Wegener's granulomatosis. Cryoglobulins are not specific for or diagnostic of any of these conditions but are one of the signs associated with them.

There are three types of cryoglobulinemia:

  • Type I, which consists of a monoclonal immunoglobulin – a single type of protein that is produced by an abnormal cloned cell. This type is often seen in people with myeloma or lymphoma.
  • Type II, which consists of a mixture of monoclonal and polyclonal immunoglobulins. This type is often seen in people with hepatitis C or other viral infections.
  • Type III, which consists of polyclonal immunoglobulins. This type is often seen in people with autoimmune diseases.

Initial testing does not distinguish between these three types of cryoglobulins, but the proteins involved can be determined through subsequent protein electrophoresis testing.

How is the sample collected for testing?

A blood sample is obtained by inserting a needle into a vein in the arm and collecting the blood in a pre-warmed tube. The sample is kept at or near body temperature during sample preparation. The person's serum is then refrigerated for 72 hours and examined daily (up to 7 days) for precipitates. If there are any present, then the quantity is estimated and the sample is warmed to determine whether the precipitates dissolve. If they do, then cryoglobulins are present.

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

No test preparation is usually needed. An 8-hour fast before sample collection may be instructed in order to minimize the potential for turbidity (cloudiness) in the sample due to triglycerides.

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Common Questions
View Sources

Sources Used in Current Review

MedlinePlus Medical Encyclopedia. Cryoglobulins. Available online at Accessed November 2013.

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Mayo Clinic. Cryoglobulinemia. Available online at through Accessed November 2013.

Vasculitis Foundation. Cryoglobulinemia. Available online at through Accessed November 2013.

Sources Used in Previous Reviews

Pagana, K. D. & Pagana, T. J. (© 2007). Mosby's Diagnostic and Laboratory Test Reference 8th Edition: Mosby, Inc., Saint Louis, MO. Pp 328-329.

Clarke, W. and Dufour, D. R., Editors (© 2006). Contemporary Practice in Clinical Chemistry: AACC Press, Washington, DC. Pp 209.

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