cryoglobulinemia 

The presence of large amounts of cryoglobulins in the blood.
Cryoglobulin is a circulating protein, specifically immunoglobulin (i.e. IgG, IgM, IgA, or light chain), that clumps together or precipitates when exposed to cold and dissolves when warmed.
They may be present in small quantities in the blood of some healthy people but are most frequently associated with abnormal protein production and a variety of diseases and conditions like inflammation and organ damage.
(Symptoms)
• bruising
• rashes, purpura
• skin ulcers
• gangrene
• joint pain, muscle pain
• weakness, fatigue
• Raynaud phenomenon
(Associated diseases)
• Infections: Lyme disease, infectious mononucleosis, hepatitis C, and HIV/AIDS
• Autoimmune diseases: systemic lupus erythematosus, rheumatoid arthritis, Sjögren syndrome
• Diseases characterized by an increase in lymphocytes: multiple myeloma, lymphoma, lymphoid leukemia
• vasculitis
• kidney disease
(Types)
• Type I: (Composition) Monoclonal IgG, IgM, IgA, or their κ or λ light chains. (Associated diseases) Hematological diseases, particularly MGUS, smoldering multiple myeloma, multiple myeloma, Waldenström's macroglobulinemia, and chronic lymphocytic leukemia.
• Type II: Most common. (Composition) Monoclonal IgM + polyclonal IgG or, rarely, IgA. (Associated diseases) Infectious diseases, particularly hepatitis C infection, HIV infection, and Hepatitis C and HIV coinfection; hematological diseases particularly B cell disorders. Autoimmune diseases.
• Type III: (Composition) Polyclonal IgM + polyclonal IgG or IgA. (Associated diseases) Autoimmune diseases, particularly Sjögren syndrome and less commonly systemic lupus erythematosus and rheumatoid arthritis. Infectious diseases, particularly HCV infection.
(Mechanisms that cryoglobulins cause tissue damage)
• Increase blood viscosity reduces blood flow to tissues to cause hyperviscosity syndrome (headache, confusion, blurry or loss of vision, hearing loss, and epistaxis).
• Deposit in small arteries and capillaries plugs these blood vessels and causes infarction and necrosis of tissues including in skin, distal extremities, and kidneys.
• Deposit on the endothelium activates the blood complement system to form pro-inflammatory elements such as C5a, initiating the systemic vascular inflammatory reaction (cryoglobulinemic vasculitis).
(cryoglobulin test)
To detect the presence and relative quantity of cryoglobulins in the blood.
The sample is kept at or near body temperature during sample preparation. It is then refrigerated for 72 hours and examined daily (up to 7 days) for precipitates. If there are any present, then the quantity is estimated and the sample is warmed to determine whether the precipitates dissolve. If they do, then it is positive. It will be followed by protein electrophoresis (immunofixation electrophoresis), that measures certain proteins to determine the type(s) of cryoglobulins and type of cryoglobulinemia.
(Treatment)
• Drugs to the underlying condition: nonsteroidal anti-inflammatory drugs (NSAIDs), corticosteroids, other immune suppressants
• plasmapheresis: In case the symptoms are severe, to reduce the amount of cryoglobulins in the blood by exchanging blood plasma for donor plasma.
Cf. cold agglutinin disease