Fibrinogen factor

Fibrinogen (factor I, 340 kDa see Figures 51-1 and 51-4 and Tables 51-1 and 51-2) is a soluble plasma glycoprotein that consists of three nonidentical pairs of polypeptide chains (Aa,Bpy)2 covalently linked by disulfide bonds. The B(3 and y chains contain asparagine-linked complex oligosaccharides. All three... 

Fibrinogen (factor I) is a large (340 kDa) glycoprotein consisting of two identical tri-polypeptide units, a, P and y. Its overall structural composition may thus be represented as (a P y)2. 

The most important reaction in blood clotting is the conversion, catalyzed by thrombin, of the soluble plasma protein fibrinogen (factor 1) into polymeric fibrin, which is deposited as a fibrous network in the primary thrombus. Thrombin (factor 11a) is a serine proteinase (see p. 176) that cleaves small peptides from fibrinogen. This exposes binding sites that spontaneously allow the fibrin molecules to aggregate into polymers. Subsequent covalent cross-linking of fibrin by a transglutaminase (factor Xlll) further stabilizes the thrombus. 

Overall, therefore, activation of the thrombolytic cascade occurs exactly where it is needed— on the surface of the clot. This is important as the substrate specificity of plasmin is poor, and circulating plasmin displays the catalytic potential to proteolyse fibrinogen, factor V and factor VIII. Although soluble serum tPA displays a much reduced activity towards plasminogen, some free circulating plasmin is produced by this reaction. If uncontrolled, this could increase the risk of subsequent haemorrhage. This scenario is usually averted, as circulating plasmin is rapidly... 

Note In fibrinolysis, plasmin, an endopeptidase that is converted from plasminogen by an activator, hydrolyzes fibrin, fibrinogen, factor V, and factor VIII to their inactive products. Hageman factor (factor XII) converts a proactivator to the active activator. Agents such as thrombin, streptokinase, and urokinase therefore enhance the formation of plasmin and hence have fibrin lytic properties. Epsilon-aminocaproic acid inhibits the activator-mediated formation of plasmin and hence may be used as an antidote to streptokinase-urokinase, or in a defibrination syndrome when bleeding from a mucous membrane occurs. 

Figure 5.3. Intrinsic and extrinsic blood clotting cascades. Factor I, fibrinogen Factor II, prothrombin (vitamin K-dependent) Factor III, thromboplastin Factor V, proac-celerin Factor VII, proconvertin (vitamin K-dependent) Factor VIII, antihemophilic factor Factor IX, Christmas factor (vitamin K-dependent) Factor X, Stnart factor (vitamin K-dependent) Factor XI, plasma thromboplastin Factor XII, Hageman factor Factor XIII, fibrin-stabilizing factor and Factor XIV, protein C (vitamin K-dependent). What was at one time called Factor IV is calcinm no factor has been assigned nnmber VI.

Thrombosis and hemorrhage are well-recognized complications in 1-2% of patients receiving asparaginase. This is due to a coagulopathy, which has been variously attributed to reduced concentrations of fibrinogen, factors IX, XI, VIII complex, antithrombin III, and plasminogen (6). 

The liver synthesizes fibrinogen factors V, VIII, XI, and XII, and the vitamin K-dependent factors II, VII, IX, and X. Furthermore the liver plays an important role in platelet growth and function. The vitamin K-dependent proteins contain y-carboxy-glutamic acid. Vitamin K is necessary for the carboxylation of these proteins, which facilitate the conversion of prothrombin to thrombin. Patients with severe hepatocellular disease have decreased synthesis of the vitamin K-dependent clotting factors, especially factor VII. Furthermore, patients with cholestatic disease have decreased bile salt secretion, which is necessary for the absorption of vitamin K, leading to failure of activation of factors II, VII, IX, and X. In these patients, unlike those with hepatocellular disease, the prothrombin time can be corrected with an injection of vitamin K. 

Factors Xa Va and Villa -< Prothrombin (factor II) -.Fibrinogen (factor I) Transglutaminase (factor XIII)... 

Proteins that do not fit into the previous functional categories are fibrinogen, factor XIII (the plasma protransglutaminase), and von Willebrand factor. 

Stief TW, Kurz J, Doss MO, Fareed J. Singlet oxygen inactivates fibrinogen, factor V, factor VIII, factor X, and platelet aggregation of human blood. Thromb Res 2000 97 473-80. 

Stief, T. W. Kurz, J. Doss, M. O. Fareed, J. Singlet Oxygen Inactivates Fibrinogen, Factor V, Factor VIII, Factor X, and Platelet Aggregation of Human Blood. Thromb. Res., 2000, 97, 473. 

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