Coagulation factor thrombin

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. 

Coagulation Factors II, III, VII, IX, X, XI, and Xlla fragments, thrombin, and plasmin are classified as serine proteases because each possesses a serine residue with neighboring histidine and asparagine residues at its enzymatically active site (Table 3). Factors II, VII, IX, and X, Protein C, Protein S, and Protein Z are dependent on the presence of vitamin K [84-80-0] for their formation as biologically functionally active procoagulant glycoproteins. 

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). 

Once injured or activated by a toxic substance (e.g., bacterial toxins, placenta chemicals, snake venom, etc.), endothelial cells and monocytes respond by generating tissue factor on the cell surface. This, in turn, leads to the generation of tissue factor-factor Villa complexes, followed by unregulated and excessive generation of thrombin, fibrin, systemic microthrombi and consumption of coagulation factors,... 

Antithrombin III. AT-III administration holds some promise because it inhibits a number of activated coagulation factors F-XIa, F-IXa, F-Xa, and thrombin. There are, however, no data to support the use of heparin. Although a... 

Figure 12.8 Binding of hirudin to thrombin, thus inactivating this activated coagulation factor...

In the extravascular pathway (right), tissue thromboplastin (factor 111), a membrane protein in the deeper layers of the vascular wall, activates coagulation factor Vll. The activated form of this (Vila) autocatalytically promotes its own synthesis and also generates the active factors IXa and Xa from their precursors. With the aid of factor Villa, PL, and Ca factor IXa produces additional Xa, which finally— with the support of Va, PL, and Ca ""—releases active thrombin. 

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. 

Mechanism of action - Argatroban is a synthetic, direct thrombin inhibitor that reversibly binds to the thrombin active site. It inhibits thrombin-catalyzed or induced reactions, including fibrin formation activation of coagulation factors V, VIII, and XIII protein C and platelet aggregation. 

Heparin binds to antithrombin III and induces a conformational change that accelerates the interaction of antithrombin III with the coagulation factors. Heparin also catalyzes the inhibition of thrombin by heparin cofactor II, a circulating inhibitor. Smaller amounts of heparin are needed to prevent the formation of free thrombin than are needed to inhibit the protease activity of clot-bound thrombin. Inhibition of free thrombin is the basis of low-dose prophylactic therapy. 

III which rapidly inhibits activated coagulation factors IXa, Xa, XIa and Xlla, plasmin, kallikrein and thrombin, thus inhibiting conversion of fibrinogen to fibrin. 

Clinical pharmacology Activated factor IX in combination with activated factor VIII activates factor X. This results ultimately in the conversion of prothrombin to thrombin. Thrombin then converts fibrinogen to fibrin, and a clot can be formed. Factor IX is the specific clotting factor deficient in patients with hemophilia B and in patients with acquired factor IX deficiencies. The administration of Coagulation Factor IX (Recombinant) increases plasma levels of factor IX and can temporarily correct the coagulation defect in these patients. 

Hematologic and coagulation factors Lepirudin-thrombin inhibitor. Hirudin-human recombinant produced Refludan Lyophilized 50 mg vial IV infusion after bolus dose... 

Other aptamers under clinical trials are for coagulation factors including thrombin, Factor VIIA, Factor IXA and Factor XII. Additional aptamers are being tested for kidney and lung cancers. A distinct advantage of aptamers is the availability of antidotes for them, which are short complementary sequences to the aptamers that serve as their antagonists and could be used to avert aptamer toxicity. 

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. 

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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