Clustering of Thrombin Generation Test Data Using a Reduced Mathematical Model of Blood Coagulation

• Published in: Acta biotheoretica Vol. 68; no. 1; pp. 21 - 43
• Main Authors: Ratto, N., Tokarev, A., Chelle, P., Tardy-Poncet, B., Volpert, V.
• Format: Journal Article
• Language: English
• Published: Dordrecht Springer Netherlands 01.03.2020; Springer Nature B.V; Springer Verlag
• Subjects: Blood Coagulation; Education; Evolutionary Biology; Family Characteristics; Hemophilia; Hemophilia A - diagnosis; Hemophilia A - physiopathology; Humans; Mathematical models; Mathematics; Models, Theoretical; Philosophy; Philosophy of Biology; Reagent Kits, Diagnostic; Regular Article; Thrombin; Thrombin - metabolism; Thrombosis; Tissue factor; Hemophilia patients; Thrombin generation test; Model reduction; Mathematical simulation
• ISSN: 0001-5342; 1572-8358
• DOI: 10.1007/s10441-019-09372-w

Correct interpretation of the data from integral laboratory tests, including Thrombin Generation Test (TGT), requires biochemistry-based mathematical models of blood coagulation. The purpose of this study is to describe the experimental TGT data from healthy donors and hemophilia A (HA) and B (HB) patients. We derive a simplified ODE model and apply it to analyze the TGT data from healthy donors and HA/HB patients with in vitro added tissue factor pathway inhibitor ( TFPI ) antibody. This model allows the characterization of hemophilia patients in the space of three most important model parameters. The proposed approach may provide a new quantitative tool for the analysis of experimental TGT. Also, it gives a reduced model of coagulation verified against clinical data to be used in future theoretical large-scale modeling of thrombosis in flow.