Test Catalog

Test ID: CRGSP    
Cryoglobulin and Cryofibrinogen Panel, Serum and Plasma

Useful For Suggests clinical disorders or settings where the test may be helpful

Evaluating patients with vasculitis, glomerulonephritis, and lymphoproliferative diseases


Evaluating patients with macroglobulinemia or myeloma in whom symptoms occur with cold exposure


This test is not useful for general screening of a population without a clinical suspicion of cryoglobulinemia.

Testing Algorithm Delineates situations when tests are added to the initial order. This includes reflex and additional tests.

If cryoglobulin has a positive result after 1 or 7 days, then immunofixation will be performed at an additional charge. Positive cryoglobulins of 0.1 mL or above of precipitate will be typed once.

Clinical Information Discusses physiology, pathophysiology, and general clinical aspects, as they relate to a laboratory test

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.

Reference Values Describes reference intervals and additional information for interpretation of test results. May include intervals based on age and sex when appropriate. Intervals are Mayo-derived, unless otherwise designated. If an interpretive report is provided, the reference value field will state this.


Negative (positives reported as percent or trace amount)

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.

Interpretation Provides information to assist in interpretation of the test results

An interpretive report will be provided.

Cautions Discusses conditions that may cause diagnostic confusion, including improper specimen collection and handling, inappropriate test selection, and interfering substances

Failure to follow specimen handling instructions may cause false-negative results.

Clinical Reference Recommendations for in-depth reading of a clinical nature

1. Kyle RA, Lust JA: Immunoglobulins and laboratory recognition of monoclonal proteins. Section III. Myeloma and related disorders. In: Wiernik PH, Canellos GP, Dutcher JP, Kyle RA, eds. Neoplastic Diseases of the Blood. 3rd ed. Churchill Livingstone; 1996:453-475

2. Desbois AC, Cacoub P, Saadoun D: Cryoglobulinemia: An update in 2019. Joint Bone Spine. 2019 Nov;86(6):707-713. doi: 10.1016/j.jbspin.2019.01.016