Flow effect on thrombus formation in stenosed coronary arteries: a computational study

Papadopoulos, Konstantinos (2015). Flow effect on thrombus formation in stenosed coronary arteries: a computational study. (Unpublished Doctoral thesis, City University London)

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Abstract

Thrombotic complications often occur in stenosed coronary artery, causing permanent damage and even death. Although the exact factors and events leading to thrombus formation are not entirely known, the local rheological conditions as well as the different tendency for clotting of the blood of each individual are considered to have an important role both in progress of the disease and the relevant complications. Recently a statistical correlation between the exact location of the stenosis and the evolution of the disease has been reported [1]. In this work we investigated whether this connection can be predicted by computational simulations.
For this purpose, a simplified model for blood coagulation, focusing mainly on thrombin activation, has been formulated in three steps. A phenomenological sub-model for thrombin generation was developed and calibrated, based on clinical tests (not laboratory experiments). The model was proved capable of reproducing with acceptable accuracy the rate of thrombin generation for blood samples from individuals with different thrombogenic potential, including haemophilia cases. A second sub-model for platelet aggregation on reacting surface was developed and calibrated in order to reproduce experimental data [2]. Finally, the whole coagulation model was adapted for application under flow conditions, based on the threshold behaviour of blood coagulation under flow in respect to wall shear rate and reacting surface stream-wise length [3].
In order to test the developed models, 3 groups of left anterior descending (LAD) geometry models have been constructed based on the location of the stenotic lesion. Each group consisted by geometries with different degrees of stenosis. Two of these groups (named MI1 and MI2) were statistically assessed as of higher risk for complications with the third one (STA) considered safer. Transient flow simulations were performed for these three groups, with representative coronary flow conditions. Flow was resolved by employing the incompressible Navier-Stokes equations for Newtonian fluid, which are considered to describe with acceptable accuracy the blood motion in arteries. Processing of the results have shown that appropriate surface quantities can distinct between high and low complication risk cases. Finally, based on the results of the healthy model and on previous works, a set of flow-based risk indices was proposed in order to distinguish among arbitrary geometries the ones that are more likely to lead to coronary artery disease complications.
Finally the developed model for coagulation was applied in selected (based on the flow simulation results) geometries for the three groups, under the previously calculated pulsating blood flow conditions. The simulation results have indicated that in geometries with higher degree of stenosis and higher wall shear values (regardless of the geometric group considered) the propagation of thrombin is slower. All MI2 models had similar behaviour: low average thrombin concentration and production rate with high thrombin concentration restricted in specific sites. On the contrary, in STA and MI1 models we could not identify a uniform pattern. In most cases high risk sites (elevated concentration and production rate of thrombin) were found near the wall at the areas of recirculation vortices formed after the stenotic lesion. Although this study showed that computational simulations can be used for the assessment of stenosed LAD and probably coronary arteries in general, it also showed that in order to obtain results that can be safely trusted for diagnosis the method should be applied on a large number of real geometries from patients with known disease outcome.

Item Type: Thesis (Doctoral)
Subjects: Q Science > QA Mathematics > QA75 Electronic computers. Computer science
R Medicine > R Medicine (General)
Divisions: School of Engineering & Mathematical Sciences
URI: http://openaccess.city.ac.uk/id/eprint/13497

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