Factor Vila

Dennis, M.S., Lazarus, R.A. Kunitz domain inhibitors of tissue factor-factor Vila. 1. Potent inhibitors selected from libraries by phage display. /. Biol. Chem. 269 22129-22136, 1994. [Pg.372]

PA S1 S01.215 Coagulation factor Vila Drug target for control of coagulation... [Pg.880]

The marine natural product dynosin A (92) is a new member of the aerugi-nosin family and a novel inhibitor of thrombin and Factor Vila. In Hanessian s total synthesis of 92 [66], both the dihydroxyoctahydroindole 88 and the A3 pyrroline moiety 91 were prepared by RCM-based routes (Scheme 17). [Pg.288]

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.)...

Activated on surface of activated platelets by tenase complex (Ca, factors Villa and IXa) and by factor Vila in presence of tissue factor and Ca. ... [Pg.600]

A glycoprotein expressed on the surface of injured or stimulated endothelial cells to act as a cofactor for factor Vila. [Pg.600]

Recombinant factor Vila may be considered as an alternative to prothrombin complex concentrate... [Pg.53]

Recombinant factor Vila has been shown to have a benefit in the treatment of ICH. The Recombinant Activated Factor VII... [Pg.172]

Intracerebral Hemorrhage Trial compared three different doses and placebo. Doses were 40,80, or 160 mcg/kg or placebo given as an IV infusion over 1 to 2 minutes within 4 hours after the onset of symptoms. Hematoma growth was decreased at 24 hours, mortality was decreased at 90 days, and overall functioning was increased at 90 days. Further studies are ongoing to evaluate the role of recombinant factor Vila in ICH treatment.41... [Pg.172]

Factor Vila (rFVIIa) is a bypassing agent designed to generate thrombin only at tissue injury sites, where it binds tissue factor and, in this manner, minimizes the risk of systemic thrombotic events. rFVIIa is used effectively in surgeries and spontaneous bleeds.14... [Pg.991]

PCCs contain the vitamin K-dependent factors II, VII, IX, and X. These agents represent another attempt to bypass the factor at which the antibody is directed (see Fig. 64-2). However, PCCs carry the risk of serious thrombotic complications. Porcine factor VIII is most useful when the inhibitor titer is less than 50 BU (see Fig. 64-2 for dose and frequency). Owing to its similarity to human factor VIII, porcine factor VIII participates in the coagulation cascade. However, most inhibitors have very weak neutralizing activity against it. Porcine factor VIII is a third-line agent (only after factor Vila and a PCC have failed) owing to a 15% incidence of cross-reactivity.15... [Pg.991]

Clotting factor Plasma proteins found in the blood that are essential to the formation of blood clots clotting factors circulate in inactive forms, but are activated by their predecessor in the clotting cascade or a thrombogenic substance. Each clotting factor is designated by a Roman numeral (e.g., factor VII) and by the letter a when activated (e.g., factor Vila). [Pg.1562]

NovoSeven Coagulation factor Vila Novo Nordisk Bleeding episodes in hemophilia A or B... [Pg.694]

The activity of factor Vila is enhanced astronomically (10 millionfold) upon binding to tissue factor. The VII or VHa-tissue factor complex activates factors IX and X and autoactivates factor VII. Although the activity of the tissue factor-factor VII complex is expressed without the presence of the negatively charged phosphatidylserine, the activity can be enhanced by its presence (9). [Pg.138]

Tissue factor pathway inhibitor (TFPI), a 42-kDa protein with three Kunitz domains, is a potent inhibitor of coagulation. It inhibits tissue factor-factor Vila complex upon binding to the active site of Kunitz domain one. Factor Xa is inhibited upon binding to the active site of the second Kunitz domain of TFPI (27). [Pg.141]

Philippou H., Adami A., Amersey R. A., Stubbs P. J., Lane D. A. A novel specific immunoassay for plasma two-chain factor Vila Investigation of F Vila levels in normal individuals and in patients with acute coronary syndromes. Blood 1997 89,767-75. [Pg.164]

Some 5-25 per cent of individuals suffering from haemophilia A develop anti-factor VIII antibodies, and 3-6 per cent of haemophilia B sufferers develop anti-factor IX antibodies. This complicates treatment of these conditions and, as mentioned previously, one approach to their treatment is direct administration of factor Vila. The therapeutic rationale is that factor Vila could directly activate the final common steps of the coagulation cascade, independently of either factor VIII or IX (Figure 12.1). Factor Vila forms a complex with tissue factor that, in the presence of phospholipids and Ca2+, activates factor X. [Pg.340]

A recombinant form of factor Vila (called NovoSeven or eptacog alfa-activated ) is marketed by Novo-Nordisk (Table 12.2). The recombinant molecule is produced in a BHK cell line, and the final product differs only slightly (in its glycosylation pattern only) from the native molecule. [Pg.340]

Purification entails use of an immunoaffinity column containing immobilized murine antifactor VII antibody. It is initially produced as an unactivated, single-chain 406 amino acid polypeptide, which is subsequently proteolytically converted into the two-chain active factor Vila complex. After sterilization by filtration, the final product is aseptically filled into its final product containers, and freeze-dried. [Pg.340]

A series of indolizidinones 274-278 were designed and synthesized to evaluate their inhibitory effect on Factor VILA (FVIIa) in comparison to thrombin (Factor Ha (Flla)), plasmin, and FXIa <2002BML2907>. [Pg.398]

Klausen, N. K., and Kornfelt, T. (1995). Analysis of the glycoforms of human recombinant factor Vila by capillary electrophoresis and high-performance liquid chromatography.. Chromatogr. A 718, 195-202. [Pg.303]

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