Pathology Handbook

Cryoprotein Studies


Cryoglobulins, cryofibrinogen, cold agglutinins, immune complexes.

Clinical Indications

Cryoproteins are proteins which form a gel or precipitate on cooling the serum or plasma and re-dissolve when warmed to 37'C.  Cryoglobulins are immunoglobulins that exhibit this phenomenon and may be either monoclonal (25%) or mixed (with (18%) or without (50%) monoclonal components).  The laboratory also tests for cryofibrinogen


On request

Specific Criteria

Cryoprotein studies are indicated in any patient showing clinical manifestations including intolerance of cold with pain in exposed area's, Raynaud's phenomenon, and skin manifestations including purpura, urticaria and ulcers.

Turnaround Time

One week


SST Serum and Plasma in Biochemistry EDTA tube


2 ml



Vacutainer gold top

Vacutainer lemon top


Patients must be bled at Southend Hospital. 

When patient is ready to be bled contact Pathology Reception to obtain cryoprotein sampling tubes. 

1.  Take first blood sample into pre-warmed yellow top (SST) tube and immediately place in sand bath at 37°C

2.  Take second blood sample into pre-warmed lemon-topped (EDTA) tube and immediately place in 37°C sand bath.  

3.  Take samples and request form (along with any other samples taken at room temperature) to Pathology within 10 minutes of collection.

Causes for Rejection

Samples not collected using pre-warmed (37°C) collection tubes, not transported in pre-warmed sand bath or delay in samples reaching laboratory. 


Normal: Negative

Monoclonal cryoglobulins may be associated with immunocytomata and are usually an IgM protein. Mixed cryoglobulins may be associated with lymphoproliferative disorders, but the majority are idiopathic.