Cryofibrinogenaemia: a study of 49 patients

Abstract

The purpose of this study was to characterize the clinical features and components of 30 patients with isolated cryofibrinogen (CF) versus those of 19 patients with combined CF and cryoglobulins (CG). Secondary forms of cryofibrinogenaemia associated with collagen disorders, infectious or malignant diseases, were significantly more frequent in patients with combined CF and CG than those with isolated CF (79 versus 47%, P = 0·02). Both groups of CF patients presented predominantly cutaneous symptoms (77% in isolated CF; 58% in combined CF + CG), and less frequently venous and/or arterial thrombosis (13% in isolated CF; 3% in combined CF + CG). Patients with idiopathic forms of CF, and particularly those without CG, suffered essentially from recurrent painful skin ulcers, mainly triggered by cold exposure. Patients with isolated CF had higher mean plasma concentrations of CF than those with combined CF + CG (1·61 ± 1·26 versus 0·82 ± 1·18 g/l, respectively; P = 0·004), but there was no correlation between the CF plasma level and either the severity of symptoms or the sensitivity to cold. In patients with isolated CF, fibronectin was suggested (by precipitation analysis) to be a major component of the cryoprecipitate, whereas immunoglobulins were rarely present (in only three out of 30 patients). By contrast, in the majority of patients (78%) with combined CF and CG, the CF consisted mainly of immunoglobulins of the same class as those characterizing the associated CG. Analysis of the CG precipitate revealed the presence of fibronectin but not fibrinogen, α1‐antitrypsin and α2‐macroglobulin. In conclusion, isolated and combined cryofibrinogenaemia are associated with different clinical signs requiring different clinical management, but there is no evidence as yet for a causal role of the cryoprecipitates in the differences observed.

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“…3 Secondary CF is associated with several diseases including connective tissue and autoimmune diseases, malignancies, infection, drugs, thromboembolic conditions, and other conditions such as chronic lung disease, acute myocardial infraction, and hypothyroidism. [3][4][5] Secondary CF is most frequently associated with connective tissue diseases (42%), followed by vasculitis (25%), malignancy (21%), and infection (12%). 6 The prevalence of CF has been estimated to be 3.4% to 13%.…”

“…The most common symptoms of CF are caused by cutaneous ischemia including ulcerations, purpura, livedo reticularis, ecchymosis, Raynaud phenomenon, perniosis of the extremities, ischemic necrosis, and gangrene. [5][6][7]9,10 Cutaneous lesions typically occur at distal extremities such as the hands, feet, ears, nose, and buttocks, and are often aggravated by exposure to cold. 11 Other symptoms include thrombosis (which occurs in 25% to 40% of patients), arthralgia, and glomerulonephritis.…”

Cryofibrinogenemia Associated with Sjoegren's Syndrome: A case of Successful Treatment with High-dose Corticosteroid

“…Cryofibrinogen, described by Korst and Kratochvil in 1955, is an abnormal protein that reversibly precipitates in plasma by cold temperatures (4 ), and redissolves upon warming to 37 (1). Cryofibrinogen is a cold insoluble complex of fibrin, fibrinogen, and fibrin split products with albumin, cold insoluble globulin, factor VIII, and other plasma proteins (2) (3)(4)(5).…”

“…Cryofibrinogen is a cold insoluble complex of fibrin, fibrinogen, and fibrin split products with albumin, cold insoluble globulin, factor VIII, and other plasma proteins (2) (3)(4)(5). It on the left fourth finger (Fig.…”

“…Because there was marked improvement of the ulcerations at 6 weeks after starting high-dose PSL (Fig. 1B) (4,(8)(9)(10)(11)(12)(13) …”