Interpretation
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.
Cryoprecipitants may be identified as:
Cryofibrinogen: This is observed as a precipitant only in the plasma tube identified at 4°C. These are rare but may be associated with vasculitis.
Cryoglobulins are classified into 3 types:
-Type I (monoclonal)
-Type II (mixed monoclonal-polyclonal)
-Type III (polyclonal)
Type I: These are purely monoclonal immunoglobulins, usually associated with MGUS, macroglobulinaemia or multiple myeloma.
Type II: These are a mixture of 2 or more immunoglobulins, of which at least one is monoclonal. This type is usually associated with autoimmune disorders, such as; vasculitis, glomerulonephritis, systemic lupus erythematosus, rheumatoid arthritis and Sjorgren’s syndrome; infections, such as hepatitis, infectious mononucleosis, cytomegalovirus and toxoplasmosis. This condition may occur in the absence of any underlying disease.
Type III: These consist of one or more polclonal immunoglobulins. Generally these are present only in trace amounts. These are generally associated with the same conditions that Type II cryoglobulins are associated with.
Failure to identify cryoglobulins or cryofibrinogen may be due to failure to follow sample collection procedures. It is imperative that these are strictly adhered to.
Reference Intervals
Assay is qualitative only so no RI available.
Test Method
The normal proteins of plasma and serum do not precipitate in the cold. An aliquot of plasma and serum are incubated for 72 hrs at 4 degrees C. If a precipitate develops, the tube(s) are warmed to 37 degrees C to check that the precipitate redissolves, then incubated again at 4 degrees C to check precipitate reforms. All positive cryoglobulins are identified by electrophoresis and immunofixation.