Cryofibrinogenaemia

Abstract

A 41-year-old woman presented with a 5-year history of arthralgia, Raynaud phenomenon and recurrent acral ulcerations that were affecting her nose, ears, fingers and feet, especially after cold exposure. Physical examination showed an erythematous nose with early ulceration (top left) and an irregularly shaped white scar (arrow) and a small haemorrhagic crust (arrowhead) of the fifth finger on the left hand (right). Laboratory findings included a normal complete blood cell count, biochemical profile and thrombophilia study with negative tests for cryoglobulinaemia, syphilis, viral hepatitis and autoantibodies. A skin biopsy from the edge of the finger ulcer showed numerous fibrin thrombi in the small dermal vessels. The above findings led us to test for a cryofibrinogen, which was demonstrated by the detection of white precipitate when the citrated plasma was maintained at 4°C for 72 h (middle, bottom of tube). This dissolved completely upon warming and was not detected in serum. The cryoprecipitate was studied by two-dimensional electrophoresis, demonstrating the α, β and γ chains of fibrinogen (bottom left). A diagnosis of essential cryofibrinogenaemia was made and the patient was treated with stanozolol, an androgen with known fibrinolytic activity, resulting in the resolution of her lesions. Cryofibrinogenaemia is defined by the presence of a reversibly cryoprecipitable protein in plasma but not in serum, together with cutaneous manifestations as well as cold sensitivity, purpura, livedo reticularis, Raynaud phenomenon, and skin ulcers or necrosis. It may be essential or secondary to an underlying disorder, such as lymphoma, carcinoma and acute infections, autoimmune and thromboembolic diseases. Cryofibrinogen is composed of fibrinogen, fibrin and smaller amounts of other proteins, which may cause thrombotic occlusion of the small arteries. In patients with otherwise unexplained skin ulcers, determination of plasma cryofibrinogen should be considered.