Cryofibrinogen, Qualitative

Cryofibrinogen is an abnormal complex of proteins that precipitate out of plasma as it is cooled.¹ These cold, insoluble protein complexes can be composed of fibrin, fibrinogen, fibrin split products, along with other plasma proteins. Cryofibrinogen forms in refrigerated plasma, but not in refrigerated serum.¹ Protein precipitate that forms in both refrigerated serum and refrigerated plasma is referred to as cryoglobulin. Testing for cryofibrinogen requires the collection of serum (see Cryoglobulin, Qualitative With Quantitative Reflex [001594]) in order to exclude the presence of cryoglobulin in the patient sample.¹ Cryofibrinogen can occur spontaneously (ie, essential cryofibrinogenemia) or in association with other inflammatory conditions. Secondary cryofibrinogenemia has been reported in patients with malignancy, diabetes mellitus, collagen vascular disease, and active infection.¹ Most individuals with cryofibrinogenemia are asymptotic.¹ Morbidity associated with cryofibrinogenemia occurs as the result of thrombotic occlusion of the small to medium arteries by insoluble protein complexes. Cryofibrinogenemia can produce symptoms due to cutaneous ischemia including purpura, livedo reticularis, ecchymosis, ulcerations, or ischemic necrosis. These symptoms are typically observed in areas of the body that tend to be at lower temperature including the hands, feet, ears, nose, and buttocks.¹ Less specific symptoms, such as malaise and fever, are also relatively common manifestations of the condition. In some rare cases, essential cryofibrinogenemia has been associated with cutaneous ulcers and gangrene.¹ Cryofibrinogenemia has infrequently been associated with other conditions including cerebrovascular thrombosis; myocardial infarction; thrombophlebitis; obstruction of the aortic, ileac, or femoral artery; pulmonary emboli; mesenteric artery thrombosis; and retinal artery thrombosis.¹ These thrombotic conditions can occasionally produce spontaneous bleeding due to depletion of clotting factors, similar to that seen in disseminated intravascular coagulation (DIC).¹