Age-related differences in thrombin generation using a mathematical model

Dlamini, Steven C. (2013) Age-related differences in thrombin generation using a mathematical model. Masters thesis, Memorial University of Newfoundland.

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Abstract

Quantitative differences in the coagulation system in children and infants, compared to adults, are well known. The purpose of this study is to investigate the coagulation system in children and infants and to examine the effect of the differences in protein levels on the resulting thrombin generation using a mathematical model. A mathematical model consisting of 77 ordinary differential equations, each representing the concentration of a specific protein, is used for this work. Thrombin-related output variables, including: endogenous thrombin potential (ETP), peak, time to peak, and initiation phase duration are presented and discussed. -- The results of the study confirm literature reports that thrombin generation in children is both delayed and reduced compared to adults. Finally, the unknown impact of quantitative differences on the potential anticoagulant drug anti-thrombin heparin (ATH) on thrombin generation is examined for all age groups. Different ATH points at which thrombin generated is satisfactorily low (less than 100 nM·sec) were found for each age group, with increasing ATH resulting in decreased thrombin generated (ETP), at a rate inversely proportional to age. The principal conclusion is that ATH has a higher ability to suppress thrombin formation in children than in adults, hence lower amounts of ATH might be needed for antithrombin therapy in children and infants.

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