At a Glance
Why Get Tested?
To determine if symptoms like sensitivity of extremities to cold is due to the presence of abnormal proteins called cryoglobulins in the blood.
When to Get Tested?
When a person has a disease which is known to be associated with cryoglobulins and has 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?
A doctor may request an 8-hour fast before sample collection.
The Test Sample
What is being tested?
This test detects and measures the relative quantity of cryoglobulins in the blood. 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 healthy people but high levels of cryoglobulins are most frequently seen with abnormal protein production associated with some autoimmune, infectious and blood diseases .
Precipitated cryoglobulins can slow the flow of blood and block small blood vessels. The presence of large amounts of cryoglobulins in the blood, called cryoglobulinaemia, can cause symptoms such as bruising, rashes, joint pain, weakness, and Raynaud's phenomenon – pain, paleness, bluing, numbness, tingling and coldness in the fingers with exposure to cold. 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 seen with a variety of conditions, including infections such as 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 chronic lymphocytic leukaemia, 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 cryoglobulins:
- Type I, which consists of a monoclonal immunoglobulin – a single type of protein that is produced by an abnormal clonal cell. This type is often seen in patients with myeloma or lymphoma.
- Type II, which consists of a mixture of monoclonal and polyclonal immunoglobulins. This type is often seen in patients with hepatitis C or other viral infections, but may also be seen with lymphoma or myeloma..
- Type III, which consists of polyclonal immunoglobulins. This type is often seen in patients with autoimmune diseases, but may also be seen in viral infections..
Initial testing does not distinguish between these three types of cryoglobulins, but the proteins involved can be determined through subsequent protein electrophoresis testing.
Cryoglobulin testing involves collecting a blood sample in a prewarmed tube and keeping the sample at or near body temperature during test preparation. The person's serum is then refrigerated for 72 hours and examined daily 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. Additional testing (protein electrophoresis) may then be undertaken to determine the specific type of cryoglobulin.
How is the sample collected for testing?
A blood sample is obtained by inserting a needle into a vein in the arm.
Is any test preparation needed to ensure the quality of the sample?
A doctor may request an 8-hour fast before sample collection to minimize the potential for turbidity in the sample due to triglycerides. There are specific laboratory requirements regarding the temperature of the specimen once the sample has been collected, and as such this test may not be available at all laboratories or collection centres.
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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.