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. Careful treatment of these developments is required. Primary cryofibrinogenemic disease
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. Very moderate cases may do well by simply avoiding cold exposure. Treatment with a corticosteroid plus low-dose aspirin followed by maintenance therapy with an anabolic steroid where necessary are recommended for moderately severe cases. Very severe cases generally require an immunosuppressive drug regimen and if extreme or life-threatening require resorting to plasmaphoresis or plasma exchange. Cryofiltration apheresis, a method to remove plasma agents by removing cold-induced precipitated material, may be an effective alternative to plasmaphoresis and plasma exchange but is still regarded as second-line therapy for cryofibirnogenemic disease treatment.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. That is, the cryofibrinoginemic disease may appear to precede by years the malignant disorder to which it is associated.
Cryofibrinogenemia refers to a condition classified as a fibrinogen disorder in which a persons 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. Return of plasma to more normal temperature resolubilizes the precipitate. Cryofibrinogenemia may occur in individuals that have no obvious evidence of precipitate-induced tissue damage (asymptomatic cryofibrinogenemia), or in consequence of cryofibrinogen precipitation resulting in blood clots in small and medium size arteries and veins. When occurring in association with another causual disease, cryofibrinogenemic disease is referred as secondary cryofibrinogenemia; in the absence of such an association, it is referred to as primary cryofibrinogenemia. Cryofibrinogen precipitation
The reasons for the cold temperature-induced in vitro as well as the in vivo precipitation of the fibrinogen-containing complex is unknown. The fibrinogen involved in precipitate formation appears to have a normal structure. This separates cryofibrinogenemia from two pathological blood-clotting/bleeding diseases that can mimic cryofibrinogenemia but are due to structurally abnormal fibrinogen viz., dysfibrinogenemia and hypodysfibrinogenemia. Based on in vitro studies, three causes have been hypothesized for the precipitate formed in cryofibrinogenemia. 1) The blood and plasma of individuals with cryofibrinogenemia lack the fibrinolysis activity that normally degrades and thereby resolubilizes the precipitate.