Fibrinogen

Fibrinogen is the most abundant coagulation protein in the blood and the first clotting protein to be discovered. It is normally converted to fibrin by thrombin in the terminal stage of blood coagulation.

Fibrinogen is comprised of three pairs of polypeptide chains - alpha, beta and gamma. Thrombin cleaves small peptides - fibrinopeptides A and B - from the fibrinogen molecule to form fibrin monomers. These monomers spontaneously polymerize to form the first visible fibrin clot. However, this fibrin polymer is unstable and susceptible to premature degradation until it has been stabilized by the action of Factor XIII.

Low levels of functional (clottable) fibrinogen may be seen during disseminated intravascular coagulation (DIC), during thrombolytic therapy, following massive hemorrhage or in association with severe liver disease. There are three types of congenital abnormaility that affect fibrinogen.

Afibrinogenemia - in which there is a complete absence of fibrinogen. Of the three types, this one causes the most serious bleeding. It may be suspected when all clotting tests (PT, APTT and thrombin time) fail to give a clot and no heparin or other tytpe of anticoagulant is present in the patient's plasma.

Hypofibrinogenemia - which is associated with reduced plasma fibrinogen levels. Bleeding problems may be mild, moderate or severe.

Dysfibrinogenemia - in which the quantity of fibrinogen is usually normal, but is defective in function. There are more than 70 different types of congenital dysfibrinogenemia. Such individuals rarely have bleeding problems; many are asymptomatic, while others are predisposed to thrombosis. Acquired dysfibrinogenemia may also occur in liver disease and is a normal physiological finding in newborn infants. Special tests will be necessary to diagnose dysfibrinogenemia.

Symptoms of afibrinogenemia include bleeding from the umbilical cord stump in newborns, bleeding in the urinary tract and intracranial hemorrhage. Treatment can include fresh frozen plasma (FFP), cryoprecipitate or fibrinogen concentrate. Because of the relatively long plasma half life of fibrinogen, weekly infusions are usually sufficient to maintain hemostasis.

Since fibrinogen is an acute phase reactant elevated levels are associated with stress or inflammation.

Fibrinogen can be assayed by taking advantage of the fact that under conditions of excess thrombin, the clotting time is proportional to the fibrinogen concentration (the Clauss method).

The normal range for plasma fibrinogen is 170 - 450 mg/dl.