Fibrinogen is one of the plasma protein factors involved in the process of blood coagulation. It is an elongated globulin with a molecular weight of about 350,000, and is synthesized only in the liver. The thrombin formed in the second stage of coagulation acts on fibrinogen to split off a peptide fragment, converting the soluble fibrinogen into insoluble fibrin, which constitutes the clot proper. The fibrino-peptide split-off from the fibrinogen molecule by the trypsin-like action of the thrombin contains some 3 per cent of the original protein nitrogen. The residual fibrinogen fibrils then aggregate and enmesh to form a three-dimensional, cross-linked fibrin gel. A transluscent colorless gel is produced from plasma, but in blood clotting the gel is red because of entrapped blood cells. On standing, the gel contracts (syneresis) to form a tougher mass, extruding serum in the process.
The plasma concentration of fibrinogen is about 200 to 400 mg./100 ml. (0.2 gm. to 0.40 gm./100 ml.); none is present in serum, since fibrinogen is removed as fibrin in the clotting process. Elevations of fibrinogen levels up to 700 mg./100 ml. are encountered in many inflammatory diseases, such as rheumatic fever, pneumonia, septicemias, and tuberculosis. An increase in the erythrocyte sedimentation rate (ESR) is intimately associated with increased plasma fibrinogen levels.
Decreased levels of plasma fibrinogen are rather uncommon. In congenital hypofibrinogenemia, very little fibrinogen is present because of a rare genetic defect that is reflected by the inability of the liver to synthesize fibrinogen. The condition of acquired hypofibrinogenemia is of most interest in clinical work. Low levels of fibrinogen may be observed as a consequence of severe liver disease, which is also associated with low levels of several other clotting factors, such as prothrombin, and Factor VII. However, low levels of fibrinogen are not clinically important in most patients with severe liver disease because liver disease that produces severe hypofibrinogenemia usually leads to rapid decline and death by other causes. The most serious cases of low fibrinogen levels are encountered in certain complications of pregnancy, and it is in connection with these conditions that the laboratory is most often asked to assay fibrinogen levels, frequently on an emergency basis. In premature separation of the placenta (antepartal hemorrhage), the high levels of thromboplastic agents present in the placenta are released into maternal blood, resulting in a rapid conversion of fibrinogen to fibrin in the blood, placenta, and other organs.
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