Analysis, detection and quantitation of mixed cryoglobulins in HCV infection: brief review and case examples

Considering the high incidence of cryoglobulins in hepatitis C virus (HCV) infection together with the high worldwide prevalence of HCV infection, identification of clinically apparent mixed cryoglobulinemia syndrome is increasingly important as most patients who are identified can now be successfully treated. Different approaches for the detection, analysis and reporting of cryoglobulins have been described and there is a wide variation in results reported, ranging from a qualitative "negative" or "positive", to a quantitative report including cryoglobulin type and the total protein. Protein and immunofixation (IFE) electrophoresis are generally used to identify and characterize cryoglobulins, as these methods quantify and phenotype. Here, we present a brief review of the literature and demonstrate a case oriented approach for identifying mixed cryoglobulinemia from the preanalytical phase, leading up to and including the analytical phase with characterization by IFE. Most patients with mixed cryoglobulinemia can now be treated with success. Nevertheless, the high cost may limit treatment of those with symptoms unless there is laboratory evidence for mixed cryoglubulinemia. Low levels of cryoglobulins can be associated with severe symptoms; as a result, accurate identification of cryoglobulins may be of increasing importance since clear identification may be a good reason to initiate treatment.