Cryoglobulin evaluation: best practice?

Ann Clin Biochem 2010;47:8-16
© 2010 Association for Clinical Biochemistry


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Review Articles

Ravishankar Sargur1,
Peter White2 and
William Egner3

1 Clinical Immunology Unit, Department of Immunology, Northern General Hospital, Herries Road, Sheffield S5 8YD;
2 Peter White, UKNEQAS;
3 William Egner, Protein Reference Unit, Department of Immunology, Northern General Hospital, Herries Road, Sheffield, S5 7AU, UK

Corresponding author: Dr Ravishankar Sargur. Email: Ravishankar.Sargur{at}

Cryoglobulins are serum immunoglobulins that precipitate attemperatures below 37°C and re-dissolve on warming. Cryoglobulinaemialeads to variable symptoms including characteristic purpura,ischaemia of extremities, renal failure, peripheral neuropathy,abdominal pain secondary to intestinal ischaemia and arthralgias.Cryoglobulin testing is underutilized in clinical practice.It has been neglected in clinical laboratories and by cliniciansdue to several factors, such as the length of time it takesfor serum cryoglobulin analysis to be performed in the laboratory,the perceived difficulty in getting optimal sampling conditionsand a failure to appreciate that even apparently low levelsof cryoglobulin can be associated with severe symptoms in somepatients. The most important variable confounding standardizationof cryoglobulin testing is improper sample handling. A recentreport critically appraising the current practice of cryoglobulinevaluation in 137 laboratories in Europe by United Kingdom NationalExternal Quality Assurance Scheme (UKNEQAS) illustrated thewide variability in practice. Although many clinical laboratoriesperform cryoglobulin evaluation, there are widespread differencesin the methodology used and the care with which this is carriedout and this leads to considerable intralaboratory and interlaboratoryvariability. The most common sources of error are false-negativeresults due to loss of cryoprecipitate during transport andstorage. Better standardization is needed to avoid missed diagnosesand improve the comparability of results. Laboratories shouldensure that sample temperature is maintained at 37°C untilthe serum is separated. In this article, we briefly review theclassification and clinical features of cryoglobulins and suggestbest practice guidelines for laboratory detection and identificationof cryoglobulins.

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