Coated platelets introduce significant delay in onset of peak thrombin production: Theoretical predictions

J Theor Biol. 2018 Sep 14:453:108-116. doi: 10.1016/j.jtbi.2018.05.021. Epub 2018 May 18.

Abstract

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%).

Keywords: Coagulation; Coated platelets; Dose-dependence; Mechanistic model; Thrombin.

Publication types

  • Research Support, Non-U.S. Gov't
  • Validation Study

MeSH terms

  • Blood Coagulation / physiology
  • Blood Platelets / cytology
  • Blood Platelets / metabolism*
  • Humans
  • Models, Theoretical*
  • Phosphatidylserines / metabolism
  • Platelet Activation / physiology*
  • Platelet Count
  • Thrombin / metabolism*
  • Time Factors

Substances

  • Phosphatidylserines
  • Thrombin