Simulated Thrombin Generation in the Presence of Surface-Bound Heparin and Circulating Tissue Factor
Name
10439_2015_Article_1377.pdf
Size
771.05 KB
Format
Adobe PDF
Checksum (MD5)
d8886458f412dbe9e0a323aa45306e59
Author(s)
Dydek, E. Victoria
Chaikof, Elliot L
Date Issued
July 2015
Journal
Annals of Biomedical Engineering
Publisher
Springer US
Citation
Dydek, E. Victoria, and Elliot L. Chaikof. “Simulated Thrombin Generation in the Presence of Surface-Bound Heparin and Circulating Tissue Factor.” Annals of Biomedical Engineering 44.4 (2016): 1072–1084.
Version
Author's final manuscript
Abstract
An expanded computational model of surface induced thrombin generation was developed that includes hemodynamic effects, 22 biochemical reactions and 44 distinct chemical species. Surface binding of factors V, VIII, IX, and X was included in order to more accurately simulate the formation of the surface complexes tenase and prothrombinase. In order to model these reactions, the non-activated, activated and inactivated forms were all considered. This model was used to investigate the impact of surface bound heparin on thrombin generation with and without the additive effects of thrombomodulin (TM). In total, 104 heparin/TM pairings were evaluated (52 under venous conditions, 52 under arterial conditions), the results demonstrating the synergistic ability of heparin and TM to reduce thrombin generation. Additionally, the role of circulating tissue factor (TF[subscript p]) was investigated and compared to that of surface-bound tissue factor (TF[subscript s]). The numerical results suggest that circulating TF has the power to amplify thrombin generation once the coagulation cascade is already initiated by surface-bound TF. TF[subscript p] concentrations as low as 0.01 nM were found to have a significant impact on total thrombin generation.
MIT Department
Harvard University--MIT Division of Health Sciences and Technology
Lincoln Laboratory
Terms of Use
Article is made available in accordance with the publisher's policy and may be subject to US copyright law. Please refer to the publisher's site for terms of use.
Persistent DSpace Link
DOI of Published Version
https://doi.org/10.1007/s10439-015-1377-5
