Coagulation factor inhibitors

Ortel TL, Charles LA, Keller FG, Marcom PK, Oldham HN Jr, Kane WH, Macik BG. Topical thrombin and acquired coagulation factor inhibitors clinical spectrum and laboratory diagnosis. Am J Hematol 1994 45(2) 128-35. 

The fluid nature of blood can be attributed to the t1at cells (endothelial) that maintain a nonthrombogenie environment in the blood vessels. This is a result of at least four phenomena (a) the maintenance of a transmural negative electric charge that prevents adhesion between platelets (h) the release of a plasmalogen activator, which activates the fibrinolytic pathway (c) the release of thrombomodulin, a cofactor that activates protein C. a coagulation factor inhibitor and (d) the release of PGU. a potent inhibitor of platelet aggregation. 

Biotextiles as medical implants Table 19.2 Coagulation factor inhibitors... 

Dewald G, Bork K Missense mutations in the coagulation factor XII (Hageman factor) gene in hereditary angioedema with normal Cl inhibitor. Biochem Biophys Res Commun 2006 343 1286-1289. 

The procoagulant factors produced by endothelial cells are the coagulation factors von Willebrand factor (WF), F-V, F-VIII, tissue factor (TF), and plasminogen activator inhibitor (PAI), which blocks the activators u-PA and t-PA and counteracts fibrinolysis (G21, FI6). It has been shown that under the influence of complement activation (C9), in response to endotoxin in vitro (C24), in experimental E. coli sepsis in baboons (D30), and after stimulation with TNF (Al, N6), endothelial cells up-regulate the expression of TF, down-regulate TM and inhibit the production of t-PA and PAF. Thus, the balance may shift in the procoagulant direction with a large excess of PAI-1. 

Volume 222. Proteolytic Enzymes in Coagulation, Fibrinolysis, and Complement Activation (Part A Mammalian Blood Coagulation Factors and Inhibitors)... 

The table also lists important globulins in blood plasma, with their mass and function. The a- and p-globulins are involved in the transport of lipids (lipoproteins see p. 278), hormones, vitamins, and metal ions. In addition, they provide coagulation factors, protease inhibitors, and the proteins of the complement system (see p. 298). Soluble antibodies (immunoglobulins see p. 300) make up the y-globulin fraction. 

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. 

Antithrombohtic eEects of razaxaban (an inhibitor of coagulation factor Xa) are currently being evaluated in Phase E trials. 

Thienopyridines incorporated into the structures of inhibitors of coagulation factor Xa show good activity and selectivity. In addition, with the presence of heteroatoms, solubility properties of the compounds are improved <1999BML2753, 2001MI83, 2006BMC1309>. 

Tetrahydropyrazolo[3,4-f]pyridines have been prepared as cannabinoid modulators <2007W0112399>. The pyra-zolo[3,4-4pyridine, Apixaban (BMS-562247), has been found to be a highly potent, selective, efficacious, and orally bioavailable inhibitor of blood coagulation factor xa <2007JMC5339>. Several pyrazolo[3,4-f]pyridines have been found to be potent inhibitors of human eosinophil phosphodiesterase <2007JMC344>. 

A new route to l-aryM-aminopyrazole-5-carboxylic acid derivatives via reacting arylhydrazononitriles with halocar-boxylic acid derivatives has recently been reported. The pyrazoles so obtained were used for synthesis of arylazolo[4,3-. 

Hematologic and coagulation factors Eptifibatide, reversible platelet aggregation inhibitor Integrilin 20mg in 10ml vial, 75 mg or 200 mg in 100 ml vial IV... 

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

Coumarins are competitive inhibitors of vitamin K, which is required for the formation in the liver of the amino acid, gamma-carboxyglutamic acid. This is necessary for the synthesis of prothrombin and factors VII, IX and X (Figure 17.1). After starting treatment the anticoagulant effect is delayed until the concentration of normal coagulation factors falls (36-72 h). The effects can be reversed by vitamin K (slow maximum effect only after 3-6 h) or by whole blood or plasma (fast). Gut bacteria synthesise vitamin K and thus are an important source of this vitamin. Consequently, antibiotics can cause excessive prolongation of the prothrombin time in patients otherwise adequately controlled on warfarin. 

Vlasuk GP. Structural and functional characterization of tick anticoagulant peptide (TAP) a potent and selective inhibitor of blood coagulation factor Xa. Thrombosis and Haemostasis 1993 70 212-216. 

Wallis RB. Inhibitors of coagulation factor Xa from macromolecular beginnings to small molecules. Current Opinion in Therapeutic Patents Aug, 1993. 

Waxman L, Smith DE, Arcuri KE, Vlasuk GP. Tick anticoagulant peptide (TAP) is a novel inhibitor of blood coagulation factor Xa, Science 1990 248 593. 

Jacobs JW, Cupp EW, Sardana M, Friedman PA. Isolation and characterization of a coagulation factor Xa inhibitor from black fly salivary glands. Thromb Haemost (GERMANY) 1990 64 235-238. 

Dunwiddie CT, Waxman L, Vlasuk GP, Friedman PA. Purification and characterization of inhibitors of blood coagulation factor Xa from hematophagous organisms. Methods in Enzymol 1993 233 291-312. 

Schreuder H, Arkema A, deBoer B, Kalk K, Dijkema R, Mulders J, Theunissen H, Hoi W. Crystallization and preliminary crystallographic analysis of antistasin, a leech-derived inhibitor of blood coagulation factor Xa. JMol Biol 1993 231 1137-1138. 

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