Factor Vila disorders

Peptide derivatives, (III), prepared by Shiraishi (3) selectively inhibited extrinsic blood coagulation by inhibiting factor Vila. a-Ketoamide peptides, (IV), while those prepared by Chatterjee (4) were effective as cysteine and serine proteases inhibitors and used in treating coagulation disorders associated with thrombophlebitis and... 

Compound 165 and its derivatives inhibit serine protease enzymes such as TF/factor Vila and Xa (tissue factor) <2004USP0235852>. Benzofurans 166 and 167, which have transposed functional groups, are both TF/factor X inhibitors. Tissue factors are involved in the release of thrombin, so these compounds are applied to the treatment of clotting disorders <2003W003082847, 2005JPP2005120080>. Diarylbenzofuran 168 is used to inhibit bone loss <1996USP5489587>. 

In general, the Factor VII activity estimated by a substrate assay correlated well with Factor VII activity determined by a clot-endpoint assay (P4, S13). However, some differences have been seen. Activation of Factor VII by kaolin or by exposure to cold temperatures (2-8°C) increased the level of clotting Factor VII by 4-7 times but bad no effect on the amount detected by the substrate assay (S9, TIO). It has been postulated that the partially carbox-ylated molecules of Factor VII present in patients plasma during anticoagulant therapy are detected by a substrate assay but not in a clot-endpoint test (P4). These differences between the two assay systems have been used to screen for hereditary Factor VII deficients and to detect the presence of Factor Vila in thrombotic disorders and in components for transfusion therapy (S13). 

Sprensen B, Ingerslev J. Whole blood clot formation phenotypes in hemophilia A and rare coagulation disorders. Patterns of response to recombinant factor Vila. J Thromb Haemost 2004 2 102-10. 

Factor IX (Christmas factor) is next in the intrinsic mechanism cascade. It can be activated either by XIa or by Vila of the tissue factor pathway. The absence of a functional factor IX leads to the inherited X-linked bleeding disorder hemophilia B which affects 1 in 30,000 males. The condition can be mild or very serious551552 and may be caused by a variety of mutations or by incorrect splicing of the messenger RNA for the 416-residue factor IX. The level of factor IX in blood increases with age, almost doubling by old age.552a... 

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