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Published on: October 12, 2012
Evaluation of cryoglobulins
U Kallemuchikkal1, P D Gorevic
1Department of Medicine, The Mount Sinai Medical Center, New York, NY 10029-6574, USA.
Insights
Cryoglobulin testing involves observing immunoglobulins that precipitate in cooled serum. Proper warm serum separation is crucial for accurate cryoglobulin screening and characterization.
Area of Science:
- Clinical Chemistry
- Immunology
- Hematology
Background:
- Cryoglobulins are immunoglobulins that precipitate upon cooling serum below core body temperature.
- Cryoglobulin screening is essential for diagnosing various conditions, but standardization remains a challenge.
Purpose of the Study:
- To describe the methodology of cryoglobulin screening and characterization.
- To highlight the critical importance of proper sample handling in cryoglobulin testing.
Main Methods:
- Cryoglobulin screening involves observing serum precipitation at low temperatures for up to 7 days.
- Characterization includes resolubilization tests, immunofixation, protein quantitation, and evaluation for specific biomarkers like rheumatoid factor and hepatitis C virus.
- Cryocrit measurement quantifies the precipitate volume percentage.
Main Results:
- The most significant factor affecting cryoglobulin test standardization is improper separation of warm serum from blood components.
- Accurate cryoglobulin identification requires a combination of precipitation observation, resolubilization, and immunochemical analysis.
Conclusions:
- Standardized cryoglobulin testing necessitates meticulous attention to sample handling, particularly warm serum separation.
- Proper methodology ensures reliable detection and characterization of cryoglobulins for clinical diagnosis.
Abstract:
Cryoglobulins are immunoglobulins that precipitate as serum is cooled below core body temperatures. A cryoglobulin screen is the observation of a serum specimen collected and separated while warm for cryoprecipitation over a period of up to 7 days. Values of the screening may be reported as a cryocrit, which is the volume percent of the precipitate compared with the total volume of serum. Further proof that the precipitate is indeed a cryoglobulin can be obtained by demonstrating resolubilization with warming and immunochemical analysis by immunofixation. Detailed characterization of cryoglobulins may also require rigorous washing of the precipitate, quantitation of total protein and immunoglobulins, and evaluation of serum for monoclonal gammopathy, rheumatoid factor activity, evidence of complement activation, and presence of hepatitis C virus seroreactivity or hepatitis C virus RNA. The single most important variable confounding standardization of cryoglobulin testing is the frequently improper separation of warm serum from other blood elements prior to screening and characterization.

