A NUMERICAL-ANALYSIS OF FACTOR-X ACTIVATION IN THE PRESENCE OF TISSUEFACTOR-FACTOR VIIA COMPLEX IN A FLOW REACTOR

A mathematical model has been developed to investigate previously obta ined experimental findings relating to the activation of factor X by s urface-bound tissue factor-factor VIIa (TF:VIIa) in a tubular flow rea ctor. In those experiments, factor X was perfused through a microcapil lary tube over a range of flow (shear) conditions and the activated pr oduct, factor Xa, was measured at the outlet of the tube using a chrom ogenic assay. In the present study, the steady-state convection-diffus ion equation with Michaelis-Menten kinetics used to describe the react ion at the wall was numerically integrated using an implicit method ba sed on linear systems of ordinary differential equations. The results from the numerical analysis indicated that shear rate directly affects both K-m and V-max. Values of K-m decreased from 151 to 16 nM as the shear rate increased from 25 to 2400 sec(-1). Additionally, there was a twofold increase in V-max from 1.4 to 3.0 pmol/cm(2)/min as the shea r rate increased from 25 to 300 sec(-1). These findings are in contras t with classical enzyme behavior and imply a direct effect of fluid fl ow on the kinetics of factor X activation.