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
A blood sample drawn from a vein in your arm
Test Preparation Needed?
The Test Sample
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.
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 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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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.
Sources Used in Current Review
MedlinePlus Medical Encyclopedia. Cryoglobulins. Available online at http://www.nlm.nih.gov/medlineplus/ency/article/003555.htm. Accessed November 2013.
MedlinePlus Medical Encyclopedia. Cryoglobulinemia. Available online at http://www.nlm.nih.gov/medlineplus/ency/article/000540.htm. Accessed November 2013.
ARUP Consult. Cryoglobulinemia. Available online at http://www.arupconsult.com/Topics/Cryoglobulinemia.html through http://www.arupconsult.com. Accessed November 2013.
Mayo Medical Laboratories. Cryoglobulin and Cryofibrinogen Panel. Available online at http://www.mayomedicallaboratories.com/test-catalog/Clinical+and+Interpretive/83659 through http://www.mayomedicallaboratories.com. Accessed November 2013.
University of Maryland Medical Center. Cryoglobulinemia. Available online at http://umm.edu/health/medical/ency/articles/cryoglobulinemia through http://umm.edu. Accessed November 2013.
Mayo Clinic. Cryoglobulinemia. Available online at http://www.mayoclinic.org/cryoglobulinemia/treatment.html through http://www.mayoclinic.org. Accessed November 2013.
Vasculitis Foundation. Cryoglobulinemia. Available online at http://www.vasculitisfoundation.org/education/forms/cryoglobulinemia/ through http://www.vasculitisfoundation.org. 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.
(Updated 2009 November) Cryoglobulinemia. ARUP Consult [On-line information]. Available online at http://www.arupconsult.com/Topics/Cryoglobulinemia.html?client_ID=LTD through http://www.arupconsult.com. Accessed November 2009.
Teitel, A. (Updated 2009 February 22). Cryoglobulins. MedlinePlus Medical Encyclopedia [On-line information]. Available online at http://www.nlm.nih.gov/medlineplus/ency/article/003555.htm. Accessed November 2009.
(Revised 2009 August 4). Detailed Guide: Waldenstrom Macroglobulinemia. American Cancer Society [On-line information]. Available online at http://www.cancer.org/docroot/CRI/CRI_2_3x.asp?dt=76 through http://www.cancer.org. Accessed November 2009.
Ainsworth, C. et. al. (Updated 2009 July 17). Cryoglobulinemia. Emedicine [On-line information]. Available online at http://emedicine.medscape.com/article/329255-overview through http://emedicine.medscape.com. Accessed November 2009.
(© 1995-2009). Cryoglobulin, Serum and Plasma. Mayo Clinic, Mayo Medical Laboratories [On-line information]. Available online at http://www.mayomedicallaboratories.com/test-catalog/print.php?unit_code=83659 through http://www.mayomedicallaboratories.com. Accessed November 2009.
Chan, A. et. al. (2008 February). Cryoglobulinaemia: clinical and laboratory Perspectives. Hong Kong Medical Journal v14 (1) [On-line information]. PDF available for download at http://www.hkmj.org/article_pdfs/hkm0802p55.pdf through http://www.hkmj.org. Accessed November 2009.
Bui, T. and Short, M. (2008 January 1). Photo Quiz, Localized Rash After Skin Exposure to Cold Temperature. American Family Physician [On-line information]. Available online at http://www.aafp.org/afp/20080101/photo.html through http://www.aafp.org. Accessed November 2009.
The John Hopkins Vasculitis Center: Cryoglobulinemia. Available online at http://vasculitis.med.jhu.edu/typesof/cryoglobulinemia.html through http://vasculitis.med.jhu.edu. Accessed November 2009.
American College of Rheumatology: HCV-Associated Arthritis. Available online at http://www.rheumatology.org/public/factsheets/diseases_and_conditions/hcvassociatedarthritis.asp?aud=pat through http://www.rheumatology.org. Accessed November 2009.
Henry's Clinical Diagnosis and Management by Laboratory Methods. 21st ed. McPherson RA and Pincus MR, eds. Philadelphia: 2007, Pp 704, 843.