Susree2018 - Effect of coated platelets on thrombin generation
Mathematical model of blood coagulation that simulates the effect of coated platelets on thrombin generation.
- Coated platelets introduce significant delay in onset of peak thrombin production: Theoretical predictions.
- Susree M, Panteleev MA, Anand M
- Journal of theoretical biology , 9/ 2018 , Volume 453 , pages: 108-116
- Department of Chemical Engineering, Indian Institute of Technology Hyderabad, Kandi, Sangareddy, 502285 Telangana, India.
- Platelets play a crucial role in the initiation, progress, termination as well as regulation of blood coagulation. Recent studies have confirmed that not all but only a small percentage of thrombin-activated platelets ("coated" platelets) exhibit procoagulant properties (namely the expression of phosphatidylserine binding sites) required for the acceleration and progress of coagulation. A mechanistic model is developed for in vitro coagulation whose key features are distinct equations for coated platelets, thrombin dose-dependence for coated platelets, and competitive binding of coagulation factors to platelet membrane. Model predictions show significant delay in the onset of peak Va production, and peak thrombin production when dose-dependence is incorporated instead of a fixed theoretical maximum percentage of coated platelets. Further, peak thrombin concentration is significantly overestimated when either fractional presence of coated platelets is ignored (by 299.4%) or when dose-dependence on thrombin is ignored (by 24.7%).
|Susree2018.xml||SBML L2V4 representation of Susree2018 - Effect of coated platelets on thrombin generation||64.07 KB||Preview | Download|
|fig5.jpg||Attempt at reproducing figure 5. Lag time is an issue. All max/peak values are approximately the same as in the publication.||17.01 KB||Preview | Download|
|Susree2018.cps||Model COPASI file. Equations encoded as listed in the publication. G_VII and G_VIIa may be missing terms (accounting for the second and third reactions listed in Table A1, although adding these terms has little effect on thrombin generation). G_RP and G_AP include Michaelis Menten kinetics but the modifier is used in the denominator instead of the substrate - changing this results in a curve with the same shape, just with a lag time of 300s longer. G_I and G_Ia appear to have Michaelis Menten kinetic terms with the substrate in the denominator. Table A1 typo: TF:VII + IIa -> 'VIIa' + IIa.||111.59 KB||Preview | Download|
|fig4.jpg||Attempt at reproducing figure 4. Curves for delta=1.0 and delta=0.12 appear to match the publication results however the lag time for delta=f(II) is about 200s too long. All max/peak values are the same as in the publication.||16.73 KB||Preview | Download|