Kremers2015 - Thrombin Inhibitor Kinetics

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Short description
Mathematical model of thrombin inhibition by ATIII, alpha-2-macroglobulin and miscellaneous serpins (a1-antitrypsin, a1-proteinase inhibitor, a1-antichymotrypsin, protease nexin-1, C1inhibitor and others).
Related Publication
  • The balance of pro- and anticoagulant processes underlying thrombin generation.
  • Kremers RM, Peters TC, Wagenvoord RJ, Hemker HC
  • Journal of thrombosis and haemostasis : JTH , 3/ 2015 , Volume 13 , Issue 3 , pages: 437-447 , PubMed ID: 25421744
  • Synapse bv, Cardiovascular Research Institute Maastricht, Maastricht University, Maastricht, the Netherlands.
  • The generation of thrombin in time is the combined effect of the processes of prothrombin conversion and thrombin inactivation. Measurement of prothrombin consumption used to provide valuable information on hemostatic disorders, but is no longer used, due to its elaborate nature.Because thrombin generation (TG) curves are easily obtained with modern techniques, we developed a method to extract the prothrombin conversion curve from the TG curve, using a computational model for thrombin inactivation.Thrombin inactivation was modelled computationally by a reaction scheme with antithrombin, α(2) Macroglobulin and fibrinogen, taking into account the presence of the thrombin substrate ZGGR-AMC used to obtain the experimental data. The model was validated by comparison with data obtained from plasma as well as from a reaction mixture containing the same reactants as plasma.The computational model fitted experimental data within the limits of experimental error. Thrombin inactivation curves were predicted within 2 SD in 96% of healthy subjects. Prothrombin conversion was calculated in 24 healthy subjects and validated by comparison with the experimental consumption of prothrombin during TG. The endogenous thrombin potential (ETP) mainly depends on the total amount of prothrombin converted and the thrombin decay capacity, and the peak height is determined by the maximum prothrombin conversion rate and the thrombin decay capacity.Thrombin inactivation can be accurately predicted by the proposed computational model and prothrombin conversion can be extracted from a TG curve using this computational prediction. This additional computational analysis of TG facilitates the analysis of the process of disturbed TG.
Submitter of the first revision: Matthew Roberts
Submitter of this revision: Matthew Roberts
Modellers: Matthew Roberts

Metadata information

isDescribedBy (1 statement)
PubMed 25421744

isPartOf (1 statement)
Gene Ontology blood coagulation

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  • Model originally submitted by : Matthew Roberts
  • Submitted: Aug 21, 2018 11:39:42 AM
  • Last Modified: Aug 21, 2018 11:39:42 AM
  • Version: 2 public model Download this version
    • Submitted on: Aug 21, 2018 11:39:42 AM
    • Submitted by: Matthew Roberts
    • With comment: Edited model metadata online.