Clinical and Interpretive

The fibrinogen assay is useful in detecting increased or decreased fibrinogen (factor I) concentration of acquired or congenital origin and for monitoring severity and treatment of disseminated intravascular coagulation and fibrinolysis.

Fibrinogen, also known as factor I, is a plasma protein that can be transformed by thrombin into a fibrin gel (“the clot”). Fibrinogen is synthesized in the liver and circulates in the plasma as a disulfide-bonded dimer of 3 subunit chains. The biological half-life of plasma fibrinogen is 3 to 5 days.

An isolated deficiency of fibrinogen may be inherited as an autosomal recessive trait (afibrinogenemia or hypofibrinogenemia) and is one of the rarest of the inherited coagulation factor deficiencies.

Acquired causes of decreased fibrinogen levels include: acute or decompensated intravascular coagulation and fibrinolysis (disseminated intravascular coagulation [DIC]), advanced liver disease, L-asparaginase therapy, and therapy with fibrinolytic agents (eg, streptokinase, urokinase, tissue plasminogen activator).

Fibrinogen function abnormalities, dysfibrinogenemias, may be inherited (congenital) or acquired. Patients with dysfibrinogenemia are generally asymptomatic. However, the congenital dysfibrinogenemias are more likely than the acquired to be associated with bleeding or thrombotic disorders. While the dysfibrinogenemias are generally not associated with clinically significant hemostasis problems, they characteristically produce a prolonged thrombin time clotting test. Congenital dysfibrinogenemias usually are inherited as autosomal codominant traits.

Acquired dysfibrinogenemias mainly occur in association with liver disease (eg, chronic hepatitis, hepatoma) or renal diseases (eg, chronic glomerulonephritis, hypernephroma) and usually are associated with elevated fibrinogen levels.

Fibrinogen is an acute phase reactant, so a number of acquired conditions can result in an increase in its plasma level:
-Acute or chronic inflammatory illnesses
-Nephrotic syndrome
-Liver disease and cirrhosis
-Pregnancy or estrogen therapy
-Compensated intravascular coagulation

The finding of an increased level of fibrinogen in a patient with obscure symptoms suggests an organic rather than a functional condition. Chronically increased fibrinogen has been recognized as a risk factor for development of arterial thromboembolism.

In patients with dysfibrinogenemias, kinetic fibrinogen assays may give spuriously low values.

The presence of large amounts of heparin (>5-10 U/mL) may cause erroneously-low kinetic estimates of fibrinogen or make it impossible to measure fibrinogen by the nephelometric end-point technique. In these cases, end-point determinations of clottable fibrinogen by a gravimetric/spectrophotometric (biuret) technique or fibrinogen immunoassay may be helpful.