Cryofibrinogenemia refers to a condition classified as a fibrinogen disorder in which a person's blood plasma is allowed to cool substantially (i.e. from its normal temperature of 37 °C to the near-freezing temperature of 4 °C), causing the (reversible) precipitation of a complex containing fibrinogen, fibrin, fibronectin, and, occasionally, small amounts of fibrin split products, albumin, immunoglobulins and other plasma proteins.
Secondary cryofibrinogenemia can develop in individuals with infection (~12% of cases), malignant or premalignant disorders (21%), vasculitis (25%), and autoimmune diseases (42%).
[6] Lymphoproliferative disorders such as B-cell lymphomas, T-cell lymphomas, chronic lymphocytic leukemia, and various plasma cell dyscrasias (e.g. multiple myeloma, Waldenström's macroglobulinemia, and the premalignant precursors to these two diseases, MGUS, smoldering multiple myeloma, IgM MGUS, and smoldering Waldenström's macroglobulinemia as well as adenocarcinomas of the stomach, liver, lung, colon, and other solid tumor cancers have been reported to be associated with symptomatic or asymptomatic cryofibrinogenemia.
Cutaneous symptoms include one or more of the following: cold contact-induced urticarial (which may be the first sign of the disease); painful episodes of finger and/or toe arterial spasms termed Raynaud phenomena; cyanosis, a palpable purpura termed cryofibrinogenemic purpura), and a lace-like purplish discoloration termed livedo reticularis all of which occur primarily in the lower extremities but some of which may occur in the nose, ears, and buttocks; non-healing painful ulcerations and gangrene of the areas impacted by the cited symptoms.
[6] Patients with secondary cryofibrinogenemia also exhibit signs and symptoms specific to the infectious, malignant, premalignant vasculitis, and autoimmune disorders associated with their disease.
[2] While rare, individuals with cryofibrinogenemic disease may experience pathological bleeding due to the consumption of blood clotting factors consequential to the formation of cryofibrinogen precipitates.
[2][6] Suggested diagnostic criteria for cryoglobulinemic disease fall into the following obligatory and additional categories:[6] The diagnosis of secondary cryofibrinogenemia also requires evidence for the cited infectious, malignant, premalignant vasculitis, and autoimmune disorders while the diagnosis of primary cryofibrinogenemia requires a lack of evidence for 1) the cited associated disorders, 2) other vascular occlusive diseases, and 3) cryoglobulinemia.
In severe cases, these individuals also risk developing serious thrombotic events which lead to tissue necrosis that may result in secondary bacterial infections and require intensive antimicrobial therapy and/or amputations.
[2][6] Success in treating the primary disease has been reported using blood clot lysing agents such as anabolic steroids (e.g. danazol or stanozolol which is no longer available in the United States), streptokinase, and streptodornase; anticoagulants such as heparin and warfarin, and immunosuppressive drug regimens such as a corticosteroid (e.g. prednisone) combined with either azathioprine of chlorambucil.
Treatment with a corticosteroid plus low-dose aspirin followed by maintenance therapy with an anabolic steroid where necessary are recommended for moderately severe cases.
[2] During the several years following its initial diagnosis, some 27 to 47% of primary cryofibrinoginemic diseases are complicated by the development of a B-cell or T-cell lymphoma.