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Cryofibrinogenemia is a rare condition caused by formation of fibrinogen, fibrin, and fibronectin complexes within the circulation. Symptoms result from vascular occlusion in cold-exposed areas. Physical examination usually reveals ulcers, livedo, and bluish-purple discolorations with crusts and scar tissue on the ears, hips, knees, fingers, and toes.

The condition is most often associated with an underlying inflammatory disorder, infection, or cancer, but familial primary cases with an autosomal dominant inheritance pattern have been described. 

Cryofibrinogenemia is diagnosed when plasma that is clear at 37°C develops a precipitate when it is cooled to 4°C. Cryofibrinogen forms a precipitate in plasma, but not in serum, because fibrinogen is consumed during clotting and is not present in serum specimens. This feature helps to distinguish cryofibrinogen from cryoglobulin. Cryoprecipitate often appears larger when collected in lithium heparin tubes than in citrate or EDTA tubes because the former contains a heparin precipitable fraction. 

Serum protein electrophoresis of the washed precipitate will show a discrete band of fibrinogen that mimics a monoclonal gammopathy, but immunofixation will not detect a monoclonal paraprotein. 

Blood should be collected into a prewarmed 37-degree 10 mL plain red top tube and a lavender (EDTA) tube. The tubes should be transported to the laboratory immediately in a thermos filled with 37-degree water.  

Reference value is absent.


Michaud M and Pourrat J. Cryofibrinogenemia. J Clin Rheumatol 2013;19:142-8. 

Moiseev S et al. Cryofibrinogenemia – a neglected disease. Rheumatology 2017;56:1445-51

Stathakis NE et al. Characterization of cryofibrinogen isolated from patients plasma. Haemostasis 1981;10:195-202.


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