Cryofibrinogens are insoluble complexes of fibrin, fibrinogen, fibrin split products, plasma proteins, and Igs that precipitate with cold exposure. They do not precipitate in serum (plasma only) because the proteins consumed in the clotting process during cooling are the necessary substrates for cryofibrinogens. It is most commonly associated with malignancy, connective tissue diseases, and infection, but has also been reported with oral contraceptive use, diabetes mellitus, and advanced atherosclerosis.
Cutaneous manifestations are the most common and are the result of vascular occlusion and tissue ischemia. They tend to occur in cold-exposed areas and include purpura, livedo, ulcers, and gangrene. Leukocytoclastic vasculitis and necrosis are seen more commonly than isolated microthrombi in biopsy specimens, but they may occur together. Thromboses in larger vessels (strokes, myocardial infarction, etc.) are seen less frequently. Paradoxical bleeding may occur due to depletion of clotting factors. There is an association with cryoglobulins: cryofibrinogens are seen in 70% of patients with cryoglobulins, whereas 60% of cryofibrinogens occur in isolation.
