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