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Cryoglobulins are immunoglobulins that precipitate when cooled and dissolve when heated. Because these proteins precipitate when cooled, patients may experience symptoms when exposed to the cold. Cryoglobulins may be associated with a variety of diseases including plasma cell disorders, autoimmune diseases, and infections. Cryoglobulins may also cause erroneous results with some automated hematology instruments.
Cryoglobulins are classified as:
-Type I (monoclonal)
-Type II (mixed--2 or more immunoglobulins of which 1 is monoclonal)
-Type III (polyclonal--in which no monoclonal protein is found)
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, systemic lupus erythematosus, rheumatoid arthritis, and Sjogren's syndrome. It may be seen in infections such as hepatitis, infectious mononucleosis, cytomegalovirus, and toxoplasmosis. Type II cryoglobulinemia may also be essential, ie, occurring in the absence of underlying disease.
Type III cryoglobulinemia usually demonstrates trace levels of cryoprecipitate, may take up to 7 days to appear, and is associated with the same disease spectrum as Type II cryoglobulinemia.
A cryoprecipitate that is seen in plasma but not in serum is caused by cryofibrinogen. Cryofibrinogens are extremely rare and can be associated with vasculitis. Due to the rarity of clinically significant cryofibrinogenemia, testing for cryoglobulins is usually sufficient for investigation of cryoproteins.
Evaluating patients with vasculitis, glomerulonephritis, and lymphoproliferative diseases
Evaluating patients with macroglobulinemia or myeloma in whom symptoms occur with cold exposure
An interpretive report will be provided.
Failure to follow specimen handling instructions may cause false-negative results.
Not useful for general screening of a population without a clinical suspicion of cryoglobulinemia.
Negative (positives reported as percent)
If positive after 1 or 7 days, immunotyping of the cryoprecipitate is performed at an additional charge.
Quantitation and immunotyping will not be performed on positive cryofibrinogen.
Kyle RA, Lust JA: Immunoglobulins and laboratory recognition of monoclonal proteins. Section III. Myeloma and related disorders. In Neoplastic Diseases of the Blood. Third edition. Edited by PH Wiernik, GP Canellos, JP Dutcher, RA Kyle. New York, Churchill Livingstone, 1996, pp 453-475