Policy on Cryoglobulin Determination


This document outlines advice which should be given by members of the Immunology laboratory concerning the collection, transport and handling of samples for ‘Cryoglobulin’ determination.

Given the complexity of procedures involved in receiving samples, performing and interpreting this test this service is not available directly to GPs.


Cryoglobulinaemia is a rare diagnosis. Only 4% of patients tested for cryoglobulins are positive. The transport and handling of cryoglobulins is difficult and is often problematic. Our experience is that >95% of samples will have a paraprotein (type I cryoglobulins), a very low C4 (type II or III cryoglobulin) or a raised rheumatoid factor (type II or III cryoglobulin) at presentation.

Therefore all requests for cryoglobulins will initially be tested for complement C4, immunoglobulins and serum electrophoresis and rheumatoid factor. Only samples with abnormal results will be considered for the cryoglobulin assay. If it is suspected that the sample was received cold then a repeat sample will be requested.

Consultant and Clinical Scientist staff in the Immunology laboratory will be happy to advise on individual patients.




Users are advised that samples which require determination of cryoglobulins should be collected by 3pm, transported to and handled in the laboratory, at 37oC.


The requesting doctor should contact Immunology reception (LGI x22117 or SJUH x64579) to inform staff that they wish to take a cryoglobulin sample. Reception staff will prepare an insulated flask containing water warmed to 37oC.

An insulated flask will be collected from Clinical Immunology Reception (Old Medical School, LGI) or Transplant Immunology Reception (Gledhow Wing, SJUH) by the requesting doctor or phlebotomist just prior to sample collection. Once the patient has been bled the sample will be immediately transported in the flask back to Reception.

Upon receipt of the cryoglobulin sample, immediately place the sample into the 37oC water bath and incubate for 30 minutes to allow the sample to clot.

Following incubation place the sample in a 30ml universal container containing approximately 10ml of water from the 37oC water bath then separate the serum by centrifugation at 3000 rpm for 10 minutes using centrifuge buckets that have been pre-warmed to 37oC in the water bath.

After centrifugation place the sample back in the 37oC water bath for 30 minutes then separate 500µL of warmed serum into a 75x13mm tube, number and place in the cryoglobulin rack in Reception Fridge 79. The primary tube is marked Cryo in felt-tip and placed in number order into a routine sample storage rack for Igs, electrophoresis, RF and C3/C4.

Alternative step for Transplant Immunology: Warm centrifuged gel-tube samples are stable and can be taken, without further warming, to Pathology reception SJUH for transfer to the LGI. For plain tube samples, aliquot warm serum into a 75x13mm tube before taking to Pathology reception. A comment must be written on the request form that the serum has been warm-separated.

Page updated: 10/10/14 | Updated by: Anna McHugh