Computational modeling of factor Xa inhibition by immobilized tissue factorpathway inhibitor
Tummala,SR; Hall,CL
Abstract Coating surfaces of implanted devices with anticoagulants can reducethrombosis and studies using a recombinant form of endogenous tissue factor pathway inhibitor(rTFPI) are promising. The anticoagulant function of immobilized rTFPI is thought to occur primarilyby its inhibition of plasma clotting factor Xa (FXa); however the kinetics of this reaction at asurface are as yet unknown. To better understand the surface inhibition reaction under flowconditions, a theoretical model was developed delineating the roles of mass transport and reactionkinetics for an in vitro parallel plate device used in prior experimental studies [Hall et al., J.Biomech. Eng. 120:484-490, 1998]. As a first approximation, the kinetics of inhibition of FXa byrTFPI reported for static, homogeneous systems was considered. The unsteady convection-diffusionequation was solved for different wall-shear rates and inlet concentrations of FXa using thecomputational fluid dynamics software CFD-ACE (ESI Software Group). The resultsshow that theheterogeneous inhibition reaction is diffusion controlled prior to saturation of the rTFPI. Theexperimental results compare favorably with the model at the lower shear rates (100-400 s(-1)). Athigher shear rates (>400 s(-1)) the theoretical results follow the same trend as the experimentalresults but show a greater inhibition of FXa, implying an effect of flow or shear on the inhibitionreaction.
Keywords Computational Biology; Factor Xa; Lipoproteins
Annals of Biomedical Engineering
0090-6964, Volume 35, Issue 3, 2007, Pages 3-418
