Clinical Pathology: Transfusion Medicine

• Cryoglobulins are immunoglobulins that precipitate at low temperatures.

• There are three types of cryoglobulins:

     1. Type I cryoglobulins are single monoclonal proteins, usually IgG or IgM. These are usually seen in Waldenström’s macroglobulinemia, multiple myeloma, and lymphoproliferative disorders.

     2. Type II cryoglobulins are monoclonal proteins, usually IgM, with a polyclonal component, usually IgG. These “mixed” cryoglobulins are usually associated with hepatitis C.

     3. Type III cryoglobulins are polyclonal immunoglobulins, usually IgG or IgM. Commonly, a polyclonal anti-IgG IgM forming precipitating immune complexes is seen. These are usually associated with hepatitis C, autoimmune diseases, and inflammatory conditions.

• The immunoglobulins and immune complexes precipitate in areas of the body exposed to lower temperatures, thereby causing small-vessel damage.

• Therapeutic plasma exchange (TPE) can be used to decrease cryoglobulin levels.

• TPE is used most often to treat severe cryoglobulinemia in patients with renal impairment, vasculitis, and/or neuropathy.

• Severe, symptomatic cryoglobulinemia is a category I indication for TPE according to the American Society for Apheresis (ASFA) guidelines published in 2013.

• Cryoglobulinemia secondary to hepatitis C is a category II indication for TPE according to the ASFA guidelines published in 2013.