Cryoglobulin clumps in cold temperatures. This physical characteristic causes people with cryoglobulin to have symptoms during cold weather: blanching, numbness, and pain in their fingers or toes (Raynaud's phenomenon); bleeding into the skin (purpura); and pain in joints (arthralgia). People with these symptoms or any other symptoms that appear in cold weather should be tested for cryoglobulin.

Diseases that cause the body to make extra or abnormal proteins are often associated with cryoglobulin. These diseases include cancers involving white blood cells, infections, autoimmune disorders, and rheumatoid diseases.

This test provides information about the cause of symptoms in a person who already has a disease process. It doesn't diagnose a specific disease or monitor the course of a disease.

This test is not a screening test for disease in a person without symptoms.

Laboratory testing for cryoglobulin is based on the fact that cryoglobulin clumps when cooled and dissolves when warmed. The test is done on a person's serum (the yellow liquid part of blood that separates from the cells after the blood clots). The serum is kept warm from the time drawn until the cells and the serum are separated in the laboratory. The serum is placed at 33.8°F (1°C) for one to seven days. If there is clumping, cryoglobulins are present. The amount of cryoglobulins is determined by measuring the amount of clumping. Negative tests are checked through seven days.

Additional testing is done to find out what kind of cryoglobulin protein is present. There are three kinds of cryoglobulin, each associated with different diseases.

The test, also called the cold sensitivity antibodies test, is covered by insurance when medically necessary. Results are usually available the following day.

This test requires 15–20 mL of blood. A healthcare worker ties a tourniquet on the person's upper arm, locates a vein in the inner elbow region, and inserts a needle into that vein. Vacuum action draws the blood through the needle into an attached tube. Collection of the sample takes only a few minutes. The blood must be kept warm, at body temperature, until the laboratory can separate the cells from the serum.

Discomfort or bruising may occur at the puncture site or the person may feel dizzy or faint. Pressure to the puncture site until the bleeding stops reduces bruising. Warm packs to the puncture site relieve discomfort.

Negative or absent.

If the person has cryoglobulin, the amount is reported. Larger amounts of cryoglobulin are associated with cancers or abnormalities involving white blood cells, moderate amounts are associated with autoimmune disorders and rheumatoid diseases, and smaller amounts are associated with infections.

The type of cryoglobulin is also reported. Type I cryoglobulin, also called monoclonal cryoglobulinemia, is found in cancers or abnormalities of white blood cells. Type II, also called mixed cryoglobulinemia, is associated with autoimmune disorders, rheumatoid diseases, and infections, particularly chronic hepatitis B.

The physician must interpret the cryoglobulin result along with other test results and the patient's clinical condition and medical history.