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Overview of cryoglobulins and cryoglobulinemia

Stanford L Peng, MD, PhD
Peter H Schur, MD
Section Editor
Mark H Wener, MD
Deputy Editor
Monica Ramirez Curtis, MD, MPH


Precipitation of blood proteins at temperatures lower than 37ºC is referred to as cryoprecipitation. Two types of cryoprecipitates are recognized. Cryoglobulin (CG) is present when proteins precipitate from an individual's serum and plasma, and cryofibrinogen refers to the precipitate from plasma only [1].

CGs are either immunoglobulins or a mixture of immunoglobulins and complement components. The nature of CGs, an overview of the clinical syndromes associated with them (cryoglobulinemia, cryoglobulinemic vasculitis), their pathogenesis, associated disorders, and prognosis are the subjects of this topic review. Treatment of cryoglobulinemia due to plasma cell disorders (monoclonal CG) and the clinical manifestations, diagnosis, and treatment of the mixed cryoglobulinemic syndromes, such as those associated with hepatitis C infection, are presented separately. (See "Treatment and prognosis of Waldenström macroglobulinemia" and "Clinical manifestations and diagnosis of the mixed cryoglobulinemia syndrome (essential mixed cryoglobulinemia)" and "Treatment of the mixed cryoglobulinemia syndrome".)

As noted above, a precipitate that develops in refrigerated plasma (cryofibrinogen) is typically composed of a mixture of fibrinogen, fibrin, fibronectin, and fibrin split products. The clinical manifestations of cryofibrinogenemia and disorders associated with the presence of circulating cryofibrinogen are discussed separately. (See "Cryofibrinogenemia".)


Cryoglobulin (CG) consists of immunoglobulins and complement components and precipitates upon refrigeration of serum and plasma. Routine laboratory testing for CG is, however, typically performed only on serum. The first description of the cryoprecipitation phenomenon has been attributed to Wintrobe and Buell, who described in 1933 a patient with signs and symptoms of hyperviscosity associated with multiple myeloma [2]. In 1947, the term “cryoglobulin” was applied to this “cold precipitable serum globulin” [3]. The appearance of precipitated CGs is illustrated in the picture (picture 1).


Although, strictly speaking, cryoglobulinemia refers to the presence of cryoglobulin (CG) in a patient's serum, this term is often used to refer to a systemic inflammatory syndrome that generally involves small-to-medium vessel vasculitis due to CG-containing immune complexes. The terms “cryoglobulinemic syndrome” and “cryoglobulinemic vasculitis” are sometimes used to make a distinction between the clinically apparent disorder and the asymptomatic presence of CGs [4-6].


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Literature review current through: Sep 2016. | This topic last updated: Aug 9, 2016.
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