Abstract Number: PB0418
Meeting: ISTH 2020 Congress
Background: Exposure of TF on the surface of cells or circulating microparticles to the blood is important for initiation of plasma coagulation. TF-dependent coagulation initiation is a multistage process, which includes the extrinsic tenase complex formation from transmembrane TF and circulating factor VIIa (FVIIa), interaction of the preferential extrinsic tenase substrate factor X (FX) with phospholipid membrane, diffusion of FX in the bloodstream or on the membrane surface, formation of ternary TF/FVIIa/FX complex and FX activation. The impact of individual reaction stages on the rate of FX activation is unclear.
Aims: Computational analysis of TF-dependent FX activation on the surface of phospholipid vesicles.
Methods: Three computational models of increasing complexity of the extrinsic tenase functioning were constructed: A, the homogeneous single-phase model, B, the homogeneous two-phase model and C, the heterogeneous model. The models were tuned to accurately describe experimental data from (Hathcock et al. 2005). The models were integrated in Matlab2012a and Comsol Multiphysics4.3a.
Results: Analysis of the models revealed that the rate-limiting stages for the FX activation depended on the TF surface densities. For high TF surface density (1000 molecules per µm2) the reaction rate was determined by the rate of FX binding to the surface. For low TF surface density (30 molecules per µm2) the reaction rate was limited by the rate of extrinsic tenase formation. In presence of vesicles without TF in the system, the heterogeneous model C described the experimental data better than the homogeneous models A and B.
Conclusions: Either the binding of FX to the vesicles or the tenase formation on the surface could be the rate-limiting stages of the tenase activity dependent on the TF surface density. In presence of vesicles without TF the rate of FX diffusion becomes of importance. The study was supported by the Russian Foundation for Basic Research grant 17-00-00138.
To cite this abstract in AMA style:Kovalenko T, Panteleev M, Sveshnikova A. Simulation of TF-dependent Factor X Activation on Phospholipid Vesicles: The Role and Importance of Individual Reaction Stages [abstract]. Res Pract Thromb Haemost. 2020; 4 (Suppl 1). https://abstracts.isth.org/abstract/simulation-of-tf-dependent-factor-x-activation-on-phospholipid-vesicles-the-role-and-importance-of-individual-reaction-stages/. Accessed March 4, 2024.
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