Simulated surface-induced thrombin generation in a flow field

S. W. Jordan, E. L. Chaikof*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

20 Scopus citations

Abstract

A computational model of blood coagulation is presented with particular emphasis on the regulatory effects of blood flow, spatial distribution of tissue factor (TF), and the importance of the thrombomodulin-activated protein C inhibitory pathway. We define an effective prothrombotic zone that extends well beyond the dimensions of injury. The size of this zone is dependent on the concentrations of all reactive species, the dimensions of TF expression, the densities of surface molecules, and the characteristics of the flow field. In the case of tandem sites of TF, the relationship between the magnitude of the effective prothrombotic zone and the interval distance between TF sites dictate the net response of the system. Multiple TF sites, which individually failed to activate the coagulation pathway, are shown to interact in an additive manner to yield a prothrombotic system. Furthermore, activation of the thrombomodulin-activated protein C pathway in the regions between sites of TF downregulate the thrombin response at subsequent TF sites. The implications of prothrombotic effects, which extend downstream beyond the discrete site of injury to interact with subsequent lesions are critical given the systemic nature of atherosclerotic disease.

Original languageEnglish (US)
Pages (from-to)276-286
Number of pages11
JournalBiophysical Journal
Volume101
Issue number2
DOIs
StatePublished - Jul 20 2011

ASJC Scopus subject areas

  • Biophysics

Fingerprint Dive into the research topics of 'Simulated surface-induced thrombin generation in a flow field'. Together they form a unique fingerprint.

Cite this