Factor VIIa

A specific immunoassay for measuring two-chain factor VIIa levels in plasma has been developed to identify activation of factor VII in patients with acute coronary syndromes suchs as myocardial infarction and unstable angina (12). Because regulation of factor VIIa is believed to be mediated by tissue factor pathway inhibitor (TFPI), its measurement is also useful in assessing thombotic and cardio-vasular disorders. Because TFPI is released by heparin, its measurement is also useful in assessing the efficacy of heparin and endothelial cell function (93). 

The protease activated receptors PAR-1 to PARA, of which PAR-1 is the thrombin receptor and PAR-2 conceivably a Factor-VIIa receptor, are particularly interesting cases. The ligands for these receptors are part of the N-terminal extension of the receptor. The enzyme (for example, thrombin) will bind and cleave off most of this extracellular segment and thereby reveal a new,... 

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. 

Considerably more is known about anticoagulants from the blood-feeding hookworm, Ancylostoma caninum. Several families of small, anti-clotting peptides have been described in A. caninum. AcAP, an 8.7 kDa peptide secreted by adult worms that does not exhibit homology to other anticoagulants, but is a potent inhibitor of Factor Xa, was described by Cappello et at. (1995). A family of related peptides, one of which uniquely inhibited a complex of blood coagulation factor VIIA and tissue factor, was also reported (Stanssens et al., 1996). 

Hordeum vulgare (barley) (Poaceae) BSZx (44 kDa) APC, Cathepsin G Chymotrypsin Cathepsin G (L355-R356), Elastase, Factors VIIa/TF, Xa, Xlla (weak), Kallikrein, Thrombin Trypsin Cathepsin G (R356-S357) [525, 526, 532]... 

A. Blood Clotting Enzyme Factor Xa, FXa, or Factor VIIa, FVIIa Inhibitors... 

Kranjc, A., Kikelj, D. and Peterlin-Masic, L. (2005) Recent advances in the discovery of tissue factor/factor, Vila inhibitors and dual inhibitors of factor, VIIa/Factor, Xa. Curr. Pharm. Des., 11, 4207 1227. 

K. J. Light, D.R. Edmunds, J.J. The discovery of fluoropyridine-based inhibitors of the factor VIIa/TE complex. Bioorg. Med. Chem. Lett. 2005, 15, 4152-4156. 

Betensley AD, Yankaskas JR. Factor viia for alveolar hemorrhage in microscopic polyangiitis. Am J Respir Grit Care Med 2002 166 1291-1292. 

The antithrombotic factors produced by endothelial cells are thrombomodulin (TM) and protein S (PS), components of the vitamin K-dependent protein C (PC) anticoagulant pathway, inhibiting F-Va-F-Villa (E15) tissue plasminogen activator (tPA), responsible for fibrinolysis (N2, LI8) and the lipoprotein-associated coagulation inhibitor (LACI), which inhibits F-VIIa-TF complex and F-Xa (B51). 

Fig. 6. Mechanism of inhibition of tissue factor pathway inhibitor (TFPI). Kunitz domain 1 (Dl) inhibits TF-VIIa complex. Domain 2 (D2) inhibits Xa.

Correlate the behavior of various solutes in superacids" with their gas-phase proton affinities. What factors besides proton affinities affect their solution chemistry Predict what species will be present when XHj (Group VA, 15). H2X (Group VIA, 16) and HX (Group VIIA. 17) are dissolved in "superacids. ... 

Factor IXa causes a rapid activation of factor X only if Ca2+, phospholipid,553 554 and the accessory factor Villa555 are present. The IXa Villa complex acts on X about 2 x 105 times faster than does IXa alone. This complex cleaves the same bonds in X as does the VIIa Va complex formed in the tissue factor pathway.514 The 2332-residue factor VIII and factor V have similar structures that include three repeats of a domain homologous to the blue copper-containing plasma protein ceruloplasmin (Chapter 16).556-559 Tyrosine 1680 of VIII apparently must be converted to a sulfate ester for full activity.560... 

A model of blood coagulation. With tissue factor (TF), factor VII forms an activated complex (VIIa-TF) that catalyzes the activation of factor IX to factor IXa. Activated factor XIa also... 

An overview of the coagulation cascade and sites of action for coumarins and heparin is shown in (A). There are two ways to initiate the cascade (B) (1) conversion of factor XII into its active form (XIIa, intrinsic system) at intravascular sites denuded of endothelium (2) conversion of factor VII into VIIa (extrinsic system) under the influence of a tissue-derived lipoprotein (tissue thromboplastin). Both mechanisms converge via factor X into a common final pathway. 

Table 2 Inhibitory activity of selected experimental pyrimidinone agents toward TF-VIIA, thrombin II, factor Xa, and trypsin II...

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