Fibrin thrombin

Xa-factor Va (prothrombinase). Tenase activates factor X and pro-thrombinase converts prothrombin to thrombin. Thrombin activates platelets and catalyzes the conversion of fibrinogen to fibrin. Thrombin also amplifies coagulation by activating factors V, VIII, and XL... 

Thrombin attacks synthetic esters, namely tosyl l-arginine methyl ester (TAMe), and when thrombin is treated with DIPT, the loss of esterase activity is proportional to the loss of clotting activity. Studies with synthetic esters have suggested that, as with trypsin, the reaction between thrombin and its substrates occurs in three steps an enzyme-substrate complex is formed the acyl portion of the ester is transferred to the enzyme, which becomes acylated while the alcoholic portion of the ester is released and the enzyme is deacylated and the peptide is transferred to water. The natural substrate of thrombin is fibrinogen. In addition to converting fibrinogen to fibrin, thrombin releases the contractile protein from platelets, activates fibrinase, and may participate in the conversion of prothrombin to thrombin. 

It can be seen from Figure 25.14 that, apart from its major role in the conversion of fibrinogen to fibrin, thrombin has an activating effect on both Factor V and Factor VIII and in this way stimulates its own production. Thrombin is also a platelet activator and increases both the size of the platelet plug and the release of platelet constituents. It also activates the fibrin-stabilizing factor (XIII) in the presence of Ca ions. 

Thrombin, the two-chain derivative of the prothrombin molecule, has a molecular weight of approximately 37,000 daltons. Its proteolytic properties induce the conversion of fibrinogen to fibrin to produce the initial visible manifestation of coagulation, the soluble fibrin clot. In addition, thrombin influences the activity of Factors V, VIII, and XIII and plasmin. Thrombin affects platelet function by inducing viscous metamorphosis and the release reaction with subsequent aggregation. 

Factor II. Prothrombin is a vitamin K-dependent compound synthesized by the Hver. When prothrombin is activated it is cleaved at two sites, resulting in a two-chain molecule linked by a disulfide bond that has a molecular weight of 37,000 daltons. Thrombin is the serine protease that initiates the conversion of soluble fibrinogen into fibrin. 

Factor XIII. Factor XIII circulates in the blood as a zymogen composed of two pairs of different polypeptide chains designated A and B. Inert Factor XIII has a molecular weight of 350,000 daltons and is converted to its active transglutaminase form in the presence of thrombin and calcium. Activated Factor XIII, Xllla, induces an irreversible amide exchange reaction between the y-glutamine and S-lysine side chains of adjacent fibrin... 

Product name (Generic, Trade Names, Manufacturer/ Distributor) Fibrin Sealant, Hemaseel APR, Haemacure, Tisseel VH, Baxter Healthcare Platelet Gel, Medtronic Harvest Technologies, and others Collagen Enhanced Fibrin Sealant, CoStasis, Cohesion Technologies, US Surgical Collagen -F Thrombin, FloSeal, Fusion Medical, Proceed Sulzer Medica... 

Fibrin sealant, thrombin and collagen, fibrin sealant plus collagen, and platelet gels... 

Prior to May of 1998 when the commercial product was approved by the FDA in the United States, surgeons in this country formed fibrin sealant by using topical bovine thrombin, which is a commercially available product, together with concentrated fibrinogen most frequently obtained from the blood bank. Standard blood bank cryoprecipitate is a good source of concentrated fibrinogen. Also... 

Daniels, T.M. and Fisher et al., PK., Antibodies to bovine thrombin and coagulation factor V associated with the use of topical bovine thrombin or fibrin glue a frequent finding. Blood, 82, 59a (1993). 

FIGURE 15.5 The cascade of activation steps leading to blood clotting. The intrinsic and extrinsic pathways converge at Factor X, and the final common pathway involves the activation of thrombin and its conversion of fibrinogen into fibrin, which aggregates into ordered filamentous arrays that become cross-linked to form the clot. 

The clear serum of this example is an amber liquid free from prothrombin, thrombin, fibrinogen and fibrin. It contains profibrinolysin and is excellently suited to further purification by salt precipitation fractionation, as given below. 

Fibrin is an elastic filamentous protein elaborated from its precursor, fibrinogen, which is present in plasma at high concentration. Fibrin is formed in response to the actions of thrombin. Thrombin cleaves small peptides from the fibrinogen molecule, forming fibrin monomers that will begin to polymerize and become crosslinked. 

---