From: Elizabeth M. Van Cott, M.D., and Michael Laposata, M.D., Ph.D., "Coagulation." In: Jacobs DS et al, ed. The Laboratory Test Handbook, 5th Edition. Lexi-Comp, Cleveland, 2001; 327-358.

Index of Tests

Cryofibrinogen [CO001200]

Applies to Cryocrit

Abstract Cryofibrinogen precipitates at cold temperatures, causing predominantly cutaneous symptoms on cold-exposed areas. It is also commonly asymptomatic.

Specimen Plasma

Container Two blue top (sodium citrate) tubes or EDTA tubes; also one red top tube for cryoglobulin. Tubes may be prewarmed to 37degrees C if necessary.

Collection Immediately place specimens in warm water and transport to laboratory.

Causes for Rejection Improper tube, specimen more than 2 hours in transit to the laboratory, specimen not warm upon arrival to laboratory

Turnaround Time 24-72 hours

Reference Interval Negative: no cryofibrinogen detected

Use Consider a cryofibrinogen assay for patients with unexplained cutaneous ulcers, ischemia or necrosis on cold-exposed areas. Occasionally, routine blood samples are noted to form a gel during or soon after blood drawing.

Contraindications Specimens containing heparin should not be used, because heparin nonspecifically precipitates fibrinogen in this assay.

Methodology Plasma is obtained by centrifuging the warm specimen at 37degrees C. The plasma is then refrigerated overnight, usually in a tube that can measure "cryocrit", such as a Wintrobe tube. To determine if fibrinogen precipitate has formed, the tube is centrifuged at 4degrees C. Each millimeter of visible precipitate represents 1% of "cryocrit" (in this case, cryofibrinogen). The cryocrit is the volume percent of the precipitate compared with the total volume of test plasma. Also, if cryofibrinogen is present, plasma fibrinogen levels are lower after refrigeration compared with fibrinogen measurements performed on the warm specimen prior to refrigeration.1 A cryoglobulin test is simultaneously performed, to ensure that the plasma precipitate is not cryoglobulin. Cryoglobulin precipitates in plasma or serum at cold temperatures, whereas cryofibrinogen precipitates in cold plasma but not serum (because fibrinogen is not present in serum). Cryoglobulin and cryofibrinogen disappear upon rewarming the specimen. See Cryoglobulin, Qualitative, Serum and Plasma.

Additional Information Cryofibrinogen consists of fibrinogen and other substances that precipitate at cold temperatures. Cryoglobulins are immunoglobulins that precipitate at cold temperatures. Cryofibrinogenemia or cryoglobulinemia both can produce cold-induced skin symptoms in the extremities, ears or nose. Such symptoms include purpura, ulceration, necrosis, gangrene, bleeding, cold urticaria, bullae, livedo reticularis, and Raynaud syndrome. In one study, 13% of cryofibrinogenemia patients had venous and/or arterial thrombosis.2 Cryofibrinogenemia can be a primary (essential) condition or it may arise in association with an underlying condition, such as malignancy, infection, inflammation, diabetes, pregnancy, scleroderma, or oral contraceptives. A few familial cases have been reported. Skin biopsies may show leukocytoclastic vasculitis.


1. Gluek HI and Herrman LG, "Cold-Precipitable Fibrinogen, Cryofibrinogen,"Arch Intern Med, 1964, 113:748-57.

2. Blain H, Cacoub P, Musset L, et al, "Cryofibrinogenaemia: A Study of 49 Patients,"Clin Exp Immunol, 2000, 120(2):253-60.


Kallemuchikkal U and Gorevic PD, "Evaluation of Cryoglobulins,"Arch Pathol Lab Med, 1999, 123(2):119-25.

Klein AD and Kerdel FA, "Purpura and Recurrent Ulcers on the Lower Extremities. Essential Cryofibrinogenemia,"Arch Dermatol, 1991, 127(1):113-8.


Comments/Questions - Report a Change - Disclaimer
This page last updated on October 21, 2010