Fibrinogen is a protein that plays a key role in blood clotting. Fibrinogen is a sticky, fibrous coagulant in the blood that appears to significantly increase the risk of experiencing one of the leading causes of death and disability - stroke.
Fibrinogen is a coagulation factor, a protein that is essential for blood clot formation. It is produced by the liver and released into the circulation as needed along with over 20 other clotting factors. Normally, when a body tissue or blood vessel wall is injured a process called the coagulation cascade activates these factors one after the other. As the cascade nears completion, soluble fibrinogen (fibrinogen dissolved in fluid) is changed into insoluble fibrin threads. These threads crosslink together to form a fibrin net and then stabilize at the injury site. The net adheres there, along with aggregated cell fragments called platelets, to form a stable blood clot. This barrier prevents additional blood loss and remains in place until the area has healed.
Fibrinogen is one of several factors that are called acute phase reactants, which means that fibrinogen levels rise sharply with conditions causing acute tissue inflammation or trauma. Fibrinogen (Factor I) is a 340 kD protein encoded on chromosome 4 and synthesised by hepatocytes. It is composed of two identical subunits, each containing three dissimilar polypeptide chains (alphaA, betaB, gammaG) which are linked by disulphide bonds. Thrombin cleaves fibrinopeptides A and B from fibrinogen, resulting in the formation of strands of insoluble fibrin monomer which consists of three paired alpha, beta and gamma chains. Afibrinogenaemia (or hypofibrinogenaemia) is due to production of decreased levels of normal fibrinogen. Dysfibrinogenaemia is a condition associated with production of structurally abnormal fibrinogen. More than 250 structural variants have been described which are associated with a bleeding tendency (Ebert RF, 1991). Most of these variants exhibit impaired thrombin-catalyzed release of fibrinopeptides, or impaired fibrin polymerization. Some variants of fibrinogen are associated with a thrombotic tendency rather than a bleeding tendency, and this has been attributed to impaired binding of plasminogen or tissue plasminogen activator to the abnormal fibrinogen molecule.
Fibrinogen is also essential for aggregation of platelets. Activation of platelets results in conformational changes in the glycoprotein IIb/IIIa membrane complex, which is subsequently able to bind plasma fibrinogen and thus cross-link adjacent platelets.
Analysis of the large-scale EUROSTROKE project (J Epidemiol Community Health 2002;56(Suppl I):i14-i18) showed that "fibrinogen is a powerful predictor of stroke" - including fatal and nonfatal strokes, first time strokes, and hemorrhagic and ischemic strokes. Dividing the population into four groups (quartiles) based on their fibrinogen levels, researchers estimated that the risk of stroke increased by nearly 50% for each ascending quartile. Individuals whose fibrinogen levels were in the highest quartile were almost seven times more likely to suffer a hemorrhagic stroke, and more than twice as likely to die from a stroke.