Cryoglobulins are proteins that reversibly precipitate or gel at 0 °C–4 °C. They are classified as follows:

1. Type I (monoclonal)

2. Type II (mixed cryoglobulins, in which a monoclonal is directed against a polyclonal immunoglobulin)

3. Type III (polyclonal, of which no monoclonal protein is found)

Types I and II are associated with monoclonal gammopathies, a group of diseases (see Immunofixation Electrophoresis [IFE], Serum and Urine) in which a monoclonal protein is produced by neoplastic plasma cells or lymphocytes. Types II and III cryoglobulins are circulating immune complexes produced in response to a variety of antigens, including viral, bacterial, and autologous antigens.

The normal proteins of serum do not precipitate in the cold. Blood should be collected, allowed to clot, and centrifuged at 37 °C. The serum should be separated at 37 °C to ensure that the cryoglobulins will remain in the serum. The serum is then refrigerated and checked each day (up to 7 days) for the presence of a white precipitate or gel. Warming the serum to 37 °C will reverse the precipitation.

The amount of cryoglobulin present can be quantified by filling a hematocrit tube with serum, incubating at 1 °C, centrifuging at 1 °C at 750 g for 30 minutes, and reading the cryocrit.

To characterize the cryoprotein, the precipitate is washed (cold saline) and redissolved (warm saline). IFE will identify the immunoglobulin classes present.

• Negative for cryoglobulin

• If positive after 3–7 days at 4 °C, IFE on the cryoprecipitate is performed to identify the protein complex.

1. Collect a 15-mL blood serum sample in a red-topped tube. Observe standard precautions. Keep the specimen at 37 °C until the cells are separated.

2. Refrigerate the serum for a minimum of 72 hours, although 7 days is better to determine the presence of a cryoglobulin.

The tendency of cryoglobulins to precipitate at low temperatures may occlude blood vessels; symptoms include Raynaud phenomenon, vascular purpura, bleeding tendencies, cold-induced urticaria, pain, and cyanosis.

Type I cryoglobulinemia is associated with monoclonal gammopathy of undetermined significance, macroglobulinemia, or multiple myeloma.

Type II cryoglobulinemia is associated with autoimmune disorders such as vasculitis, glomerulonephritis, SLE, RA, and Sjögren syndrome. It may also be seen in diseases such as hepatitis, IM, CMV, and toxoplasmosis.

Type III cryoglobulinemia is usually associated with the same disease spectrum as type II and may take the full 7 days to appear.

A cryoprecipitate in plasma but not serum is caused by cryofibrinogen. Cryofibrinogens are rare and can be associated with vasculitis.

Pretest Patient Care

1. Explain test purpose and procedure.

2. Follow guidelines in Chapter 1 for safe, effective, informed pretest care.