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This article waslast modified on 11 February 2022.
At a Glance
Why Get Tested?

To determine if symptoms such as sensitivity of extremities to cold are due to the presence of abnormal proteins called cryoglobulins in the blood.

When To Get Tested?

When a person has 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 taken from a vein in your arm, kept at body temperature until tested in the laboratory..

Test Preparation Needed?

None required

On average it takes 7 working days for the blood test results to come back from the hospital, depending on the exact tests requested. Some specialist test results may take longer, if samples have to be sent to a reference (specialist) laboratory. The X-ray & scan results may take longer. If you are registered to use the online services of your local practice, you may be able to access your results online. Your GP practice will be able to provide specific details.

If the doctor wants to see you about the result(s), you will be offered an appointment. If you are concerned about your test results, you will need to arrange an appointment with your doctor so that all relevant information including age, ethnicity, health history, signs and symptoms, laboratory and other procedures (radiology, endoscopy, etc.), can be considered.

Lab Tests Online-UK is an educational website designed to provide patients and carers with information on laboratory tests used in medical care. We are not a laboratory and are unable to comment on an individual's health and treatment.

Reference ranges are dependent on many factors, including patient age, sex, sample population, and test method, and numeric test results can have different meanings in different laboratories.

For these reasons, you will not find reference ranges for the majority of tests described on this web site. The lab report containing your test results should include the relevant reference range for your test(s). Please consult your doctor or the laboratory that performed the test(s) to obtain the reference range if you do not have the lab report.

For more information on reference ranges, please read Reference Ranges and What They Mean.

What is being tested?

This test detects and sometimes measures the relative quantity of cryoglobulins in the blood. Cryoglobulins are circulating proteins, specifically immunoglobulins, (i.e., IgG, IgM, IgA) 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 do not cause disease. In affected individuals they are most frequently associated with abnormal protein production and numerous underlying diseases and conditions.

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'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, and cause inflammation, leading to damage to organs such as the kidneys.

Cryoglobulins may be seen with a variety of conditions, including infections e.g. hepatitis C, autoimmune diseases e.g. Sjögren’s syndrome, and cancers e.g. multiple myeloma. 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 monoclonal immunoglobulin – a single type of protein that is produced by an abnormal clone of immunoglobulin-producing cell (B cell). This type can be seen in patients with myeloma or lymphoma.
  • Type II, consists of a mixture of monoclonal and polyclonal immunoglobulins. This type can be seen in patients with hepatitis C or other viral infections.
  • Type III, which consists of polyclonal immunoglobulins. This type can be seen in patients with autoimmune diseases.

Cryoglobulin testing involves collecting a blood sample into a prewarmed tube and keeping the sample at body temperature (37°) during test preparation. The person's serum is then refrigerated for at least 72 hours and examined for precipitate. After 72 hours, if precipitate is found to be present, then the quantity is estimated and the sample is warmed to determine whether the precipitate dissolves. If it does, then cryoglobulins are present.

This initial testing does not distinguish between the three types of cryoglobulin. Further testing, such as protein electrophoresis and immunofixation, quantification of immunoglobulins, complement and rheumatoid factor can be done on the warmed sample. For accurate diagnosis, it is important that the type of cryoglobulin is determined.

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Common Questions
  • How is it used?

    A cryoglobulin test is used to help detect the presence and relative quantity of cryoglobulins in the blood. It may be requested along with other tests to help identify or rule out potential causes of cryoglobulinemia. The tests requested depend on what condition or disease is suspected. They may include tests such as rheumatoid factor (RF), antinuclear antibody (ANA), and a variety of other autoantibodies to help identify or rule out an autoimmune disorder, hepatitis C testing, etc.

    If the cryoglobulin test is positive, then it will be followed with specialised protein electrophoresis and immunofixation electrophoresis (IFE) testing to determine which type(s) of protein are present as cryoglobulins and which type of cryoglobulinemia the person has.

  • When is it requested?

    The cryoglobulin test is requested whenever a person has symptoms that may be associated with cryoglobulinemia. Some of these may include:

    • Bruising
    • Rashes
    • Joint pain
    • Weakness
    • Raynaud's phenomenon, which is characterised by pain, paleness, bluing, numbness, tingling and coldness in the fingers and toes with exposure to cold.

    Cryoglobulins may sometimes cause damage to the skin that leads to ulcers and, in severe cases of tissue damage, can cause gangrene.

  • What does the test result mean?

    The cryoglobulin test is negative in most healthy people and is not routinely requested on those without symptoms.

    When the test is positive, it means that cryoglobulins are present and have the potential to precipitate upon exposure to cold. The symptoms experienced when this happens will vary from person to person, may be different with each exposure, and will not necessarily correlate with the quantity of cryoglobulins present.

    A positive test for cryoglobulin may be seen in numerous conditions. Some examples include:

  • Is there anything else I should know?

    Cryoglobulinemias are sometimes separated into "secondary" cryoglobulinemia, associated with an underlying condition, and "essential or idiopathic" cryoglobulinemia, not associated with another disease. Many of the cases of essential cryoglobulinemia have now been shown to have a disease association, such as Hepatitis C.

  • Can someone prevent cryoglobulin-related symptoms?

    Avoiding contact with cold objects and exposure to cold can help prevent or minimise symptoms.

  • Is there something I can do to get rid of my cryoglobulins?

    In general, no. If they are due to a temporary condition, such as an infection, then they may go away when the infection resolves. If they are due to a chronic condition, such as an autoimmune disorder, then they may reduce as a consequence of treating the underlying condition, but many persist. In type I cryoglobuinaemia, effective treatment of the underlying immune cell cancer will reduce the amount of cryoglobulin in the blood. In some cases, apheresis may be performed to remove cryoglobulins from the blood and to relieve symptoms, but this may help only temporarily.

  • What are some other tests that may be done to determine the underlying cause of cryoglobulinemia?

    In addition to protein electrophoresis and, depending on the doctor's suspicions about the underlying condition, other tests that may be performed include hepatitis C tests, ANA, Mono test and RF, complement C4 levels to name a few.

  • How is cryoglobulinemia treated?

    It is primarily treated by addressing the underlying condition. Drugs such as nonsteroidal anti-inflammatory drugs (NSAIDs), corticosteroids, and other immune suppressants may sometimes be needed to help relieve symptoms and minimise complications. Some patients may be suitable for B-cell depletion therapy (Rituximab).