Cryofibrinogenemia.

Cryofibrinogenemia is a cryoprotein that was first identified in 1955 by Korst and Kratochvil. Unlike cryoglobulin, the precipitate forms only in plasma and not in the serum. The presence of cryofibrinogen in plasma can be asymptomatic. Cryofibrinogenemia is considered a rare disorder: its prevalence varies from 0% to 7% in healthy subjects and from 8% to 13% in hospitalized patients. Nevertheless, cryofibrinogenemia, when a cryopathy is clinically suspected, has been reported in 12% to 51% of patients. Skin manifestations are usually the first signs and are usually moderate; in addition, cold intolerance, Raynaud phenomenon, purpura, or livedo reticularis often occurs. Skin necrosis, acral ulcers, and gangrene can lead to surgery and amputation. Systemic manifestations are common, and arterial or venous thrombotic events are frequent. Cryofibrinogenemia may be primary (essential) or secondary to other underlying disorders, such as carcinoma, infection, vasculitis, collagen disease, or associated with cryoglobulinemia. The histological features of cryofibrinogenemia can confirm the presence of cryofibrinogen within small and medium arteries, plus occlusive thrombotic diathesis composed of eosinophilic refractile deposits within vessel lumina. Cryofibrinogenemia is a treatable and potentially reversible disease.In moderate forms, it can be treated by simply avoiding cold temperatures. The use of corticosteroids in association with low-dose aspirin is the treatment of choice for moderate forms, although stanozolol is an alternative maintenance therapy. Immunosuppressive therapies, plasmapheresis, and/or intravenous fibrinolysis are useful at treating severe forms of cryofibrinogenemia. The use of anticoagulants is limited to the management of thrombotic events. Treatment of secondary cryofibrinogenemia involves the management of associated diseases. Regular follow-ups are needed because of the high risk of recurrence. Moreover, up to half of patients with cryofibrinogenemia considered as essential may develop lymphomas in the following years. Compared with cryoglobulinemia, less is known about cryofibrinogenemia. Its diagnosis should be considered when suggestive clinical manifestations are present and when there are specific biopsy findings. Although identification of cryofibrinogen in blood samples is simple and inexpensive, cryofibrinogenemia can be asymptomatic, and a lack of diagnosis criteria can make diagnosis difficult to confirm. This review describes the clinical manifestations and the biological and pathological features and discusses the criteria used to diagnose and manage cryofibrinogenemia.