Cryoglobulins, cryofibrinogenemia, and pyroglobulins

Cryoglobulins are immunoglobulins (Igs) that precipitate out of solution below core body temperatures, either as a single isotype (simple cryoglobulins) or as immune complexes in which both antibody and antigen are Igs (mixed cryoglobulins). Mixed cryoglobulins are cold-precipitable rheumatoid factors (RFs), with the serum often being positive when standard assays for IgM antiglobulin activity are used. Although many clinical laboratories offer cryoglobulin determinations, rarely is testing rigorously carried out, and there is considerable interlaboratory variability. A search for cryofibrinogenemia may be dictated by unexplained thrombohemorrhagic coagulopathy or cold-dependent purpura; it may also be dictated by the finding of characteristic pathology, occurring in various affected organs, as for example an occlusive thrombotic diathesis due to eosinophilic deposits within vessel lumina, extending into the intima, which may be associated with a granulomatous vasculitic component. Cryofibrinogenemia can be screened by cryoprecipitating or freeze-thawing plasma collected in citrate that contains an inhibitor of thrombin generation and is most convincing in the absence of coexisting cryoglobulinemia. Recognition of the laboratory phenomenon of pyroglobulinemia has importance as a potentially confounding factor for heat-based assays used to inactivate complement or to measure fibrinogen levels. Proper identification of a pyroglobulin as being a monoclonal component may in turn lead to the diagnosis of macroglobulinemia or plasma cell dyscrasia.