Thrombin blood coagulation

Dismption of the endothehal surface of blood vessels expose coUagen fibers and connective tissue. These provide surfaces that promote platelet adherence, platelet release reaction, and subsequent platelet aggregation. Substances Hberated from the platelets stimulate further platelet aggregation, eg, adenosine diphosphate maintain vasoconstriction, eg, serotonin and participate in blood coagulation, eg, platelet Factors III and IV. In addition, the release reaction modifies platelet membranes in a manner that renders phosphoHpid available for coagulation. The thrombin [9002-04-4] elaborated by the coagulation mechanism is a potent agent in the induction of the platelet release reaction. 

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 51-1. The pathways of blood coagulation. The intrinsic and extrinsic pathways are indicated. The events depicted below factor Xa are designated the final common pathway, culminating in the formation of cross-linked fibrin. New observations (dotted arrow) include the finding that complexes of tissue factor and factor Vila activate not only factor X (in the classic extrinsic pathway) but also factor IX in the intrinsic pathway, in addition, thrombin and factor Xa feedback-activate at the two sites indicated (dashed arrows). (PK, prekallikrein HK, HMW kininogen PL, phospholipids.) (Reproduced, with permission, from Roberts HR, Lozier JN New perspectives on the coagulation cascade. Hosp Pract [Off Ed] 1992Jan 27 97.)...

This is a dry sponge of human fibrin prepared by elotting a foam of human fibrinogen solution with human thrombin. It is then freeze-dried, cut into shapes and sterilized by dry heat at 130°C for 3 hours. Before use, it is saturated with thrombin solution. Blood coagulation occurs in contact with the thrombin in the interstices of the foam. 

Hirudin is a leech-derived anticoagulant that functions by directly inhibiting thrombin. A range of blood-sucking animals contain substances in their saliva that specifically inhibit some element of the blood coagulation system (Table 12.4). 

Thrombin is a serine protease and is one of the key enzymes in the blood coagulation system. It plays fundamental roles in the human body, but the major interest is in the control of throm-... 

It is believed that heparin acts by neutralizing a number of active blood coagulation factors, thus disrupting the transformation of prothrombin into thrombin. Heparin is used to prevent thrombo-formation in myocardial infarctions, thrombosis, and embolism, for maintaining liquid conditions in the blood in artificial blood drcnlation and hemodialysis. Synonyms of this drug are arteven, hepalen, leparan, Uquemin, panheprin, vetren, and many others. 

Pharmacology The antithrombotic activity is the result of antithrombin III (ATIII)-mediated selective inhibition of Factor Xa. Neutralization of Factor Xa interrupts the blood coagulation cascade and thus inhibits thrombin formation and thrombus development. 

Trifluoromethyl ketones are also powerful inhibitors of proteases of the trypsin family (trypsin, thrombin, enzymes of blood coagulation). " ... 

Mectianism of Action A factorXa inhibitor and pentasaccharide that selectively binds to antithrombin, and increases its affinity for factor Xa, thereby inhibiting factor Xa and stopping the blood coagulation cascade. Therapeutic Effect Indirectly prevents formation of thrombin and subsequently the fibrin clot. 

Mechanism of Action A blood modifier that interferes with blood coagulation by blocking conversion of prothrombin to thrombin and fibrinogen to fibrin Therapeutic Effect Prevents further extension of existing thrombi or new clot formation. Has no effect on existing clots. 

The blood coagulation cascade. Each of the curved red arrows represents a proteolytic reaction, in which a protein is cleaved at one or more specific sites. With the exception of fibrinogen, the substrate in each reaction is an inactive zymogen except for fibrin, each product is an active protease that proceeds to cleave another member in the series. Many of the steps also depend on interactions of the proteins with Ca2+ ions and phospholipids. The cascade starts when factor XII and prekallikrein come into contact with materials that are released or exposed in injured tissue. (The exact nature of these materials is still not fully clear.) When thrombin cleaves fibrinogen at several points, the trimmed protein (fibrin) polymerizes to form a clot. 

The enzymes that participate in blood clotting also are activated by partial proteolysis, which again serves to keep them in check until they are needed. The blood coagulation system involves a cascade of at least seven serine proteases, each of which activates the subsequent enzyme in the series (fig. 9.2). Because each molecule of activated enzyme can, in turn, activate many molecules of the next enzyme, initiation of the process by factors that are exposed in damaged tissue leads explosively to the conversion of prothrombin to thrombin, the final serine protease in the series. Thrombin then cuts another protein, fibrin, into peptides that stick together to form a clot. 

The key role played by the thrombin in the blood coagulation process has led to its extensive study and mainly to the understanding of its complex formation from its zymogen, prothrombin. 

Nicolaes GA, Thomassen MC, Tans G, Rosing J, Hemker HC. Effect of activated protein C on thrombin generation and on the thrombin potential in plasma of normal and APC-resistant individuals. Blood Coagul Fibrinolysis 1997 8(l) 28-38. 

Greenberg, C. S., Miraglia, C. C., Rickies, F. R., and Shuman, M. A. (1985). Cleavage of blood coagulation factor XIII and fibrinogen by thrombin during in vitro clotting. J. Clin. Invest. 75, 1463—1470. 

The process of blood coagulation is no longer considered to be a simple transformation of fibrinogen to fibrin by the action of thrombin. Rather, this remarkably complex process is a... 

Naito K, Fujikawa K, Activation of human blood coagulation factor XI independent of factor XII factor XI is activated by thrombin and factor Xia in the presence of negatively charged surfaces. J Biol Chem 1991 66 7353-7358. 

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