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

Authors
  • Susree, M1
  • Panteleev, Mikhail A2
  • Anand, M3
  • 1 Department of Chemical Engineering, Indian Institute of Technology Hyderabad, Kandi, Sangareddy, 502285 Telangana, India. , (India)
  • 2 Center for Theoretical Problems of Physicochemical Pharmacology, Federal Research and Clinical Center of Pediatric Hematology, Oncology and Immunology, Lomonosov Moscow State University, Moscow, Russia.
  • 3 Department of Chemical Engineering, Indian Institute of Technology Hyderabad, Kandi, Sangareddy, 502285 Telangana, India. Electronic address: [email protected] , (India)
Type
Published Article
Journal
Journal of Theoretical Biology
Publisher
Elsevier
Publication Date
May 18, 2018
Volume
453
Pages
108–116
Identifiers
DOI: 10.1016/j.jtbi.2018.05.021
PMID: 29782929
Source
Medline
Keywords
License
Unknown

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%).

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