Cryoglobulins are immunoglobulins which reversibly precipitate in the cold. Type I (monoclonal) cryoglobulins are associated with B-cell lymphoma and myeloma whilst mixed cryoglobulins (type II and III) are associated with infective and inflammatory disorders. Type II and Type III cryoglobulins exhibit rheumatoid factor activity and are invariably associated with marked consumption of C4. Type I cryoglobulins are usually monoclonal IgM or IgG proteins, Cryoglobulinaemia is usually a laboratory finding. Rarely, it is associated with precipitation of the immunoglobulins in vivo during very cold weather causing severe vasculitis. Unless samples to be tested for cryoglobulins are kept at 37°C from venepuncture until they are received in the laboratory the results may be meaningless. This is time consuming and problematic. As such, requests for cryoglobulins will initially be tested for C4, immunoglobulin levels (including electrophoresis) and rheumatoid factor using a routine SST sample. Only samples with abnormal results will be tested for cryoglobulins. The laboratory will then arrange for samples for cryoglobulin determination to be collected appropriately. Other cryoprecipitates can include cold agglutinins which are IgMs associated with certain infections e.g mycoplasma, listeria, rickettsia or EBV or cryofibrinogen (rarely). EDTA plasma must be used for accurate detection of crofibrinogen.
Vasculitis, renal failure, Hepatitis C, paraproteinaemia, neuropathy. Consider cryoglobulinaemia in any patient with unexplained renal or skin disease and low C4.
Type I cryoglobulinaemia: monoclonal IgG or IgM rarely IgA. C4 levels normal or low (25% cryoglobulin cases).
Type II cyroglobulinaemia: Monoclonal IgG or IgM (usually IgMk) associated with polyclonal IgG. High level of rheumatoid factor and usually very low C4 (18% cases).
Type III cryoglobulinaemia: the most common. No paraprotein but polyclonal IgM, IgG and sometimes IgA. High level of rheumatoid factor and low C4 (50% cases).
For cryoglobulin assay, sample must be collected and transported at 37°C. Sample is centrifuged and serum collected. On arrival in laboratory C3, C4, electrophoresis and Rf assays carried out on warmed sample. Remainder is cooled to 4°C Cryoglobulin will precipitate in 1-2 days. Cryoglobulin quantitated and may be analysed further by elctrophoresis.
For cryoglobulin screen, routine SST sample. For cryoglobulin assay, sample must be collected and transported at 37°C. Sample is centrifuged and serum collected.
Qualitative (semi-quantitative cryocrit).
Assay range notes
Reported as cryocrit.
7 – 14 days
Immunology The James Cook University Hospital