Cryofibrinogen

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Subject: Cryofibrinogen

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Definition

  • Cryofibrinogen is an abnormal complex of proteins that precipitate out of plasma as it is cooled. These cold, insoluble protein complexes can be composed of fibrin, fibrinogen, and fibrin split products, in conjunction with other plasma proteins. If refrigerated serum and plasma both form a precipitate, then the precipitated proteins are referred to as cryoglobulins (see below). If, however, precipitation develops after refrigeration of plasma but does not occur in cold serum, the plasma precipitate is referred to as cryofibrinogen. 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. Morbidity associated with cryofibrinogenemia occurs as the result of thrombotic occlusion of the small to medium arteries by insoluble protein complexes. Most individuals with cryofibrinogenemia are asymptomatic.

  • Normal range:

    • Negative: No precipitate at 72 hours refrigerated; quantitation and immunotyping are not generally performed on positive cryofibrinogen.

Use

  • Patients with unexplained cutaneous ulcers, ischemia, or necrosis on cold-exposed areas

  • Evaluating patients with vasculitis, glomerulonephritis, and lymphoproliferative diseases

Interpretation

Increased In

  • Vasculitis

  • Hematologic and solid neoplasms

  • Thromboembolic conditions

  • Multiple myeloma

  • Scleroderma

  • Transient benign condition associated with infection

  • Oral contraceptives

Limitations

  • If heparin is used as an anticoagulant in blood collection tubes, it may complex with fibrinogen, fibrin, and fibronectin and leads to falsely positive results. Therapeutically administered heparin may also produce false-positive results. Therefore, collected blood should be anticoagulated with EDTA, citrate, or oxalate and maintained at 37°C until the plasma is collected.

  • Fasting specimen recommended. Proper collection and transport of specimen is critical to the outcome of the assay.

  • May cause erroneous WBC count when performed on electronic cell counter.

Suggested Reading

Nash  JW, Ross  P Jr, Neil Crowson  A The histopathologic spectrum of cryofibrinogenemia in four anatomic sites. Skin, lung, muscle, and kidney. Am J Clin Pathol.  2003;119: 114–122.
 
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