Cryoglobulin

Immunology

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Description

Cryoproteins are serum proteins which reversibly precipitate at temperatures below 37C. There are two types of cryoproteins; cryoglobulins and cryofibrinogens. Cryoglobulins are immunoglobulins which precipitate in both serum and plasma whereas cryofibrinogens, which contain fibrinogen-fibrin complexes, only precipitate in plasma. Cryoglobulins can be further subclassified, according to their immunochemical composition, using the Brouet classification system [1,2]. Cryoglobulins are found in a wide spectrum of disorders but are often transient during viral or bacterial infection. Cryoprotein studies are indicated in any patient showing clinical manifestations which include intolerance of cold with pain in exposed areas. Clinical manifestations affect the skin, peripheral nerves and most seriously the kidneys. Type I monoclonal cryoglobulins are invariably associated with haematological disorders such as multiple myeloma or Waldenstrom's macroglobulinaemia. Mixed cryoglobulins, either with (Type II) or without (Type III) a monoclonal component, are associated infections, autoimmune diseases, immune-complex vasculitis and liver disease. There is a strong association between hepatitis C virus infection and mixed cryoglobulinaemia [3].

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Indications

Low C4 with features of Vasculitis. Hepatitis C Infection. Renal Disease. Paraproteinaemia. Cold induced symptoms.

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Sample Type

2 x 2mL EDTA and 2 x 2mL serum (6mL yellow tube) at 37C. Transport to laboratory from ward/OPD at 35 - 41C is essential. Laboratories referring cryoglobulin: separate samples at 35 - 41C and send at ambient temperature, store at 4C if not sent on date centrifuged.

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Reference Range

Normal sera have no cryoglobulins or at most only a trace of polyclonal cryoglobulins <0.5g/L.

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Turnaround Time

Within 1 week

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Testing Frequency

Weekly

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External Notes

Discuss with Clinical Scientist/Medical Staff. May need to repeat the test for up to 5 times if the clinical suspicion is high, as cryoglobulins are very sensitive to ambient temperature during collection and transport and false negatives are well recognised. For requests at the NGH site, obtain flask & thermometer for transport from the Immunology laboratory. For requests at the RHH site, obtain the flask & thermometer for transport from Clinical Chemistry reception (G floor).

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References

Sargur R, White P and Egner W. Cryoglobulin evaluation: best practice? Ann Clin Biochem. 2010. 47:8-16. [Ref 1]
Vermeersch P et al. A critical appraisal of current practise in the detection, analysis, and reporting of cryoglobulins. Clinical Chemistry. 2008. 54:39-43. [Ref 2].
Sansonno D et al. Hepatitis C virus infection, cryoglobulinemia, and beyond. Rheum. 2007. 46:572-578. [Ref 3]
Tedeschi A, Barate C, Minola E & Morra E. Cryoglobulinemia. Blood Rev. 2007. 21:183-200.
Gorevic P D & Galanakis. Cryoglobulins, Cryofibrinogens and Pyroglobulins. Manual of Clinical Laboratory Immunology. 6th Ed. 2002.
Kallemuchikkal U, Gorevic PD. Evaluation of cryoglobulins. Arch Pathol Lab Med. 1999. 123:119-125

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