Cryoglobulins are proteins (immunoglobulins) which precipitate out of serum at temperatures lower that normal body temperature. Although some cryoglobulins precipitate at temperatures as high as 30-35°C. in the laboratory, samples are cooled to 4°C to test for cryoglobulins. Cryoglobulinaemia is primarily a laboratory diagnosis identifying abnormal immunoglobulins or immune complexes which might precipitate in specific circumstances e.g in small capillaries in vivo. Rarely, in some patients, cryoglobulins may precipitate out in vivo in extremities e.g fingers, noses during very cold weather and in exposed locations.

Cryoglobulinaemia is a rare diagnosis. Less than 1 in 100 of first-time samples sent to the laboratory for cryoglobulin determination are positive. The transport and handling of cryoglobulins is difficult, time consuming and is often problematic. Unless samples are maintained at 37°C during transport to the laboratory, the results may be meaningless. Even a drop in sample temperature of a few degrees might result in loss of cryoglobulin particularly in blood tubes containing gel (SST tubes).

Most cryoglobulin tests are unnecessary because other tests, not needing special transport of samples, will rule out cryoglobulinaemia as a diagnosis. An initial request (cryoglobulin screen) for rheumatoid factor, C3, C4 and paraprotein determination (immunoglobulins and protein electrophoresis) on a routine sample, will show whether cryoglobulinaemia is a likely diagnosis.

Our experience is that >95% of samples which contain a cryoglobulin will have a paraprotein (type I or II cryoglobulin), a very low C4 (type II or III cryoglobulin) or a high rheumatoid factor (type II or III cryoglobulin). Staff in the Immunology laboratory will be happy to advise on individual patients.

Collection and transport of samples for cryoglobulin determination
Cryoglobulin screen – no special precautions are needed. This sample should be taken into the normal yellow top SST (gel containing) tube. On WEBICE tick the box marked Cryoglobulin screen.
If the cryoglobulin screen indicates that cryoglobulin is likely the laboratory will suggest on the report that the requestor contacts the laboratory (extension 54129) to arrange collection of a thermos flask containing sand at 37°C for transport of the sample to the laboratory.

Cryoglobulin confirmation and quantitation
Where there is laboratory evidence or strong clinical suspicion of cryoglobulinaemia, a semi-quantitative cryoglobulin assay will be carried out. The requestor must contact the laboratory (extension 54129) to arrange collection of the thermos flask containing sand at 37°C. Samples should be collected into a warm Red Top (no gel) tube and then placed immediately into the Thermos flask and transferred IMMEDIATELY the Immunology laboratory at 37°C for cryoglobulin confirmation and quantitation

Note
The significance of cryofibrinogen is very unclear and we regard this test to be of no value.