Cryofibrinogenemia is an acquired vascular occlusive disease that results from the cold precipitation of cryofibrinogens. Cryofibrinogens are composed of a complex of fibrin, fibrinogen, fibrin split products, albumin, plasma proteins, and immunoglobulins that reversibly precipitate in the cold. These cryoproteins cause an occlusive vasculopathy of small- to medium-size blood vessels. While many patients are asymptomatic, cryofibrinogenemia can cause significant morbidity. The clinical examination and course is similar to type I cryoglobulinemia. Cryofibrinogenemia can be idiopathic (primary) or associated with malignancy (particularly prostatic cancer, other solid organ tumors, and lymphomas), viral infection, collagen vascular disease, thromboembolic disease, or oral contraceptive pills.

A familial autosomal dominant form has also been reported. In a 2020 study, cryofibrinogenemia was detected in two-thirds of 54 patients with COVID chilblains. More studies are needed to confirm that cryofibrinogenemia is implicated in the pathogenesis of chilblains in COVID-19 patients.

Cryofibrinogenemia may be treatable and reversible, with a relatively prompt resolution of skin lesions with immunosuppressive therapy.