Skip to main content
SpringerLink
Log in

A Mechanistic Model of Acute Platelet Accumulation in Thrombogenic Stenoses

  • Published:
Annals of Biomedical Engineering Aims and scope Submit manuscript

Abstract

Thrombosis on an atherosclerotic lesion can cause heart attack or stroke. Thrombosis may be triggered by plaque rupture or erosion, creating a thrombogenic stenosis. To measure and model this situation, collagen-coated stenoses have been exposed to nonanticoagulated blood in a baboon ex vivo shunt. The maximum rate of platelet accumulation, measured using a gamma camera, was highest in the throat region of moderate and severe stenoses, and increased with increasing stenosis severity. A species transport model of platelet accumulation was developed, which included mechanisms of convection, shear-enhanced diffusion, near-wall platelet concentration, and a kinetic model of platelet activation and aggregation. The model accurately reproduced the average spatial pattern and time rate of platelet accumulation in the upstream and throat regions of the stenosis, where shear-enhanced diffusivity increased platelet transport in the stenosis throat. Downstream of the throat where flow is complicated by recirculation, the model computed a transport-limited region with lower than measured platelet accumulation, suggesting that fluid-phase platelet activation may significantly affect both transport and adhesion rates in the poststenotic region. This model may provide an initial quantitative estimate of the likelihood of occlusive thrombus in individual patients due to plaque erosion, artery spasm, incomplete angioplasty, or plaque rupture. © 2001 Biomedical Engineering Society.

PAC01: 8717Aa, 8719Tt, 8719Xx

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Aarts, P. A., S. A. van den Broek, G. W. Prins, G. D. Kuiken, J. J. Sixma, and R. M. Heethaar. Blood platelets are concentrated near the wall and red blood cells, in the center in flowing blood. Arteriosclerosis (Dallas)8:819–824, 1988.

    Google Scholar 

  2. Arbustini, E., B. Dal Bello, P. Morbini, A. P. Burke, M. Bocciarelli, G. Specchia, and R. Virmani. Plaque erosion is a major substrate for coronary thrombosis in acute myocardial infarction. Heart82:269–272, 1999.

    Google Scholar 

  3. Badimon, L., and J. J. Badimon. Mechanisms of arterial thrombosis in nonparallel streamlines: platelet thrombi grow on the apex of stenotic severely injured vessel wall. Experimental study in the pig model. J. Clin. Invest.84:1134–1144, 1989.

    Google Scholar 

  4. Basmadjian, D.The effect of flow and mass transport in thrombogenesis. Ann. Biomed. Eng.18:685–709, 1990.

    Google Scholar 

  5. Bluestein, D., C. Gutierrez, M. Londono, and R. T. Schoephoerster. Vortex shedding in steady flow through a model of an arterial stenosis and its relevance to mural platelet deposition. Ann. Biomed. Eng.27:763–773, 1999.

    Google Scholar 

  6. Bluestein, D., L. Niu, R. T. Schoephoerster, and M. K. Dewanjee. Fluid mechanics of arterial stenosis: relationship to the development of mural thrombus. Ann. Biomed. Eng.25:344–356, 1997.

    Google Scholar 

  7. Boreda, R., R. S. Fatemi, and S. E. Rittgers. Potential for platelet stimulation in critically stenosed carotid and coronary arteries. J. Vasc. Invest.1:26–37, 1995.

    Google Scholar 

  8. Cao, J., and S. E. Rittgers. Particle motion within in vitro models of stenosed internal carotid and left anterior descending coronary arteries. Ann. Biomed. Eng.26:190–199, 1998.

    Google Scholar 

  9. Chaitman, B. R., L. D. Fisher, M. B. Bourassa, K. Davis, W. J. Rogers, C. Maynard, D. H. Tyras, R. L. Berger, M. P. Judkins, I. Ringqvist, M. B. Mock, and T. Killip. Effect of coronary bypass surgery on survival patterns in subsets of patients with left main coronary artery disease. Report of the collaborative Study in Coronary Artery Surgery (CASS). Am. J. Cardiol.48:765–777, 1981.

    Google Scholar 

  10. Constantinides, P.Cause of thrombosis in human atherosclerotic arteries. Am. J. Cardiol.66:37G-40G, 1990.

    Google Scholar 

  11. Davies, M. J.A macro and micro view of coronary vascular insult in ischemic heart disease. Circulation82:II38-II46, 1990.

    Google Scholar 

  12. Davies, M. J., and A. C. Thomas. Thrombosis and acute coronary artery lesions in sudden cardiac ischemic death. N. Engl. J. Med.310:1137–1140, 1984.

    Google Scholar 

  13. Eckstein, E. C., and F. Belgacem. Model of platelet transport in flowing blood with drift and diffusion terms. Biophys. J.60:53–69, 1991.

    Google Scholar 

  14. Elwood, P. C., S. Renaud, D. S. Sharp, A. D. Beswick, J. R. O'Brien, and J. W. Yarnell. Ischemic heart disease and platelet aggregation. The Caerphilly Collaborative Heart Disease Study. Circulation83:38–44, 1991.

    Google Scholar 

  15. European Carotid Surgery Trialists' Collaborative Group.MRC European Carotid Surgery Trial: Interim results for symptomatic patients with severe (70–99%) or with mild (0–29%) carotid stenosis. Lancet337:1235–1243, 1991.

    Google Scholar 

  16. Executive Committee for the Asymptomatic Carotid Atherosclerosis Study.Endarterectomy for asymptomatic carotid artery stenosis. J. Am. Med. Assoc.273:1421–1428, 1995.

    Google Scholar 

  17. Feichter, J. Numerical study of platelet transport in flowing blood. MS. thesis. Georgia Institute of Technology, Atlanta, 1998, 76 pp.

    Google Scholar 

  18. Folie, B. J., and L. V. McIntire. Mathematical analysis of mural thrombogenesis. Concentration profiles of platelet-activating agents and effects of viscous shear flow. Biophys. J.58:1121–1141, 1989.

    Google Scholar 

  19. Folts, J. D., E. B. Crowell, Jr., and G. G. Rowe. Platelet aggregation in partially obstructed vessels and its elimination with aspirin. Circulation54:365–370, 1976.

    Google Scholar 

  20. Hand, N. M., D. Blythe, and P. Jackson. Antigen unmasking using microwave heating on formalin fixed tissue embedded in methyl methacrylate. J. Cell. Pathol.1:31–37, 1996.

    Google Scholar 

  21. Hanson, S. R., H. F. Kotze, B. Savage, and L. A. Harker. Platelet interactions with Dacron vascular grafts. A model of acute thrombosis in baboons. Arteriosclerosis (Dallas)5:595–603, 1985.

    Google Scholar 

  22. Huang, P. Y., and J. D. Hellums. Aggregation and disaggregation kinetics of human blood platelets: Part II. Shear-induced platelet aggregation. Biophys. J.65:344–353, 1993.

    Google Scholar 

  23. Lam, J. Y., J. G. Latour, J. Lesperance, and D. Waters. Platelet aggregation, coronary artery disease progression and future coronary events. Am. J. Cardiol.73:333–338, 1994.

    Google Scholar 

  24. Markou, C. P., S. R. Hanson, J. M. Siegel, and D. N. Ku. The role of high wall shear rate on thrombus formation in stenoses. Advances in Bioengineering, New Orleans, LA: ASME, 1993, pp. 555–558.

    Google Scholar 

  25. North American Symptomatic Carotid Endarterectomy Trial Collaborators.Beneficial effect of carotid endarterectomy in symptomatic patients with high-grade carotid stenosis. N. Engl. J. Med.325:445–453, 1991.

    Google Scholar 

  26. Sakariassen, K. S., R. Muggli, and H. R. Baumgartner. Measurements of platelet interaction with components of the vessel wall in flowing blood. Methods Enzymol.169:37–70, 1989.

    Google Scholar 

  27. Savage, B., P. R. McFadden, S. R. Hanson, and L. A. Harker. The relation of platelet density to platelet age: survival of low-and high-density 111Indium-labeled platelets in baboons. Blood68:386–393, 1986.

    Google Scholar 

  28. Siegel, J. M., C. P. Markou, D. N. Ku, and S. R. Hanson. A scaling law for wall shear rate through an arterial stenosis. J. Biomech. Eng.116:446–451, 1994.

    Google Scholar 

  29. Sorensen, E. N., G. W. Burgreen, W. R. Wagner, and J. F. Antaki. Computational simulation of platelet deposition and activation: I. Model development and properties. Ann. Biomed. Eng.27:436–448, 1999.

    Google Scholar 

  30. Sorensen, E. N., G. W. Burgreen, W. R. Wagner, and J. F. Antaki. Computational simulation of platelet deposition and activation: II. Results for Poiseuille flow over collagen. Ann. Biomed. Eng.27:449–458, 1999.

    Google Scholar 

  31. Strony, J., A. Beaudoin, D. Brands, and B. Adelman. Analysis of shear stress and hemodynamic factors in a model of coronary artery stenosis and thrombosis. Am. J. Physiol.265:H1787–1796, 1993.

    Google Scholar 

  32. Sukavaneshvar, S., G. M. Rosa, and K. A. Solen. Enhancement of stent-induced thromboembolism by residual stenoses: contribution of hemodynamics [see comments]. Ann. Biomed. Eng.28:182–193, 2000.

    Google Scholar 

  33. Sundell, I. B., U. M. Marzec, A. B. Kelly, N. A. Chronos, L. C. Petersen, S. R. Hanson, U. Hedner, and L. A. Harker. Reduction in stent and vascular graft thrombosis and enhancement of thrombolysis by recombinant Lys-plasminogen in nonhuman primates. Circulation96:941–948, 1997.

    Google Scholar 

  34. Thaulow, E., J. Erikssen, L. Sandvik, H. Stormorken, and P. F. Cohn. Blood platelet count and function are related to total and cardiovascular death in apparently healthy men. Circulation84:613–617, 1991.

    Google Scholar 

  35. Torvik, A., A. Svindland, and C. F. Lindboe. Pathogenesis of carotid thrombosis. Stroke20:1477–1483, 1989.

    Google Scholar 

  36. Trip, M. D., V. M. Cats, F. J. van Capelle, and J. Vreeken. Platelet hyperreactivity and prognosis in survivors of myocardial infarction. N. Engl. J. Med.322:1549–1554, 1990.

    Google Scholar 

  37. Turitto, V. T., and H. R. Baumgartner. Platelet deposition on subendothelium exposed to flowing blood: mathematical analysis of physical parameters. Trans. Am. Soc. Artif. Intern. Organs21:593–601, 1975.

    Google Scholar 

  38. Turitto, V. T., H. J. Weiss, and H. R. Baumgartner. The effect of shear rate on platelet interaction with subendothelium exposed to citrated human blood. Microvasc. Res.19:352–365, 1980.

    Google Scholar 

  39. Vaishnav, R. N., D. J. Patel, H. B. Atabek, M. D. Deshpande, F. Plowman, and J. Vossoughi. Determination of the local erosion stress of the canine endothelium using a jet impingement method. J. Biomech. Eng.105:77–83, 1983.

    Google Scholar 

  40. Wagner, W. R., and J. A. Hubbell. Local thrombin synthesis and fibrin formation in an in vitro thrombosis model result in platelet recruitment and thrombus stabilization on collagen in heparinized blood. J. Lab. Clin. Med.116:636–650, 1990.

    Google Scholar 

  41. Wootton, D. M. Mechanistic modeling of occlusive arterial thrombosis. PhD thesis. Georgia Institute of Technology, Atlanta, 1998, 421 pp

    Google Scholar 

  42. Young, D. F., and F. Y. Tsai. Flow characteristics in models of arterial stenoses. II. Unsteady flow. J. Biomech.6:547–559, 1973.

    Google Scholar 

  43. Zydney, A.and C. Colton. Augmented solute transport in the shear flow of a concentrated suspension. PhysicoChemical Hydrodynamics10:79–96, 1988.

    Google Scholar 

Download references

Author information

Authors and Affiliations

  1. G. W. Woodruff School of Mechanical Engineering, Georgia Institute of Technology, USA

    David M. Wootton & David N. Ku

  2. Department of Medicine, Emory University School of Medicine, Atlanta, GA

    Christos P. Markou & Stephen R. Hanson

  3. Department of Biomedical Engineering, Emory University School of Medicine, Atlanta, GA

    Stephen R. Hanson

Authors
  1. David M. Wootton
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Christos P. Markou
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Stephen R. Hanson
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. David N. Ku
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Cite this article

Wootton, D.M., Markou, C.P., Hanson, S.R. et al. A Mechanistic Model of Acute Platelet Accumulation in Thrombogenic Stenoses. Annals of Biomedical Engineering 29, 321–329 (2001). https://doi.org/10.1114/1.1359449

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1114/1.1359449

Search

Navigation