OBJECTIVE The platelet receptor for von Willebrand factor, the glycoprotein Ib-IX (GPIb-IX) complex, mediates platelet adhesion at sites of vascular injury and transmits signals leading to platelet activation. von Willebrand factor/GPIb-IX interaction sequentially activates the Src family kinase Lyn (SFK), phosphoinositide 3-kinase (PI3K), and Akt, leading to activation of integrin α(IIb)β(3) a...

Using standard one stage clotting assays the concentrations of factors II, VII, IX and X were determined in 37 patients stabilised on warfarin for between three months and 17 years. Contrary to popular belief, the concentrations were not equally depressed, with factor X the lowest, factor II at intermediate value, factors VII and IX the highest. Some 71% of the variance of the British corrected...

Thrombosis and/or disseminated intravascular coagulation (DIC) are complications specifically associated with the use of factor IX complex in some patients. Assuming that these complications might result from zymogen overload, we have produced, using diethylaminoethyl (DEAE)-Sephadex (Pharmacia, Piscataway, NJ) and sulfated dextran chromatography, a factor IX concentrate (coagulation factor IX)...

A study to compare the kinetics of activation of factor IX by Factor XIa/Ca2+ and by Factor Vlla/tissue factor/Ca2+ has been undertaken. When purified human proteins, detergent-extracted brain tissue factor and tritiated-activation-peptide-release assays were utilized, the kinetic constants obtained were: Km = 310 nm, kcat = 25 min-' for Factor XIa and Km = 210 nM, keat. = 15 min-' for Factor V...

The propeptide of human coagulation factor IX (FIX) directs the gamma-carboxylation of the first 12 glutamic acid residues of the mature protein into gamma-carboxyglutamic acid (Gla) residues. The propeptide is normally removed before secretion of FIX into the blood. However, mutation of Arg-4 in the propeptide abolishes propeptide cleavage and results in circulating profactor IX in the blood. ...

Factor IX has been expressed to high levels within a recombinant host cell and the biologically active fraction subsequently purified to homogeneity for characterization. The coding sequence for Factor IX was inserted into a mammalian cell expression vector and transfected into dihydrofolate reductase-deficient Chinese hamster ovary cells. The integrated DNA was amplified to a high copy number ...

A partial gene product was identified in a pedigree with hemophilia B due to a partial deletion of the Factor IX gene (Chen, S.-H.,S. Yoshitake, P.F. Chance, G.L. Bray, A.R. Thompson, C.R. Scott, and K. Kurachi, 1985, J. Clin. Invest., 76:2161-2164). Levels of this mutant protein in plasma of affected family members studied ranged from 24 to 36 ng/ml (0.6-0.9 U/dl or percent of normal) by a sol...

In vitro hydroxylation of aspartic acid has recently been demonstrated in a synthetic peptide based on the structure of the first epidermal growth factor domain in human factor IX (Gronke, R. S., VanDusen, W. J., Garsky, V. M., Jacobs, J. W., Sardana, M. K., Stern, A. M., and Friedman, P. A. (1989) Proc. Natl. Acad. Sci. U.S.A. 86, 3609-3613). The putative enzyme responsible for the posttransla...