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Computational Model of Device-Induced Thrombosis and Thromboembolism

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Abstract

A numerical model of thrombosis/thromboembolism (T/TE) is presented that predicts the progression of thrombus growth and thromboembolization in low-shear devices (hemodialyzers, oxygenators, etc.). Coupled convection–diffusion-reaction equations were solved to predict velocities, platelet agonist (ADP, thromboxane A2, and thrombin) concentrations, agonist-induced and shear-induced platelet activation, and platelet transport and adhesion to biomaterial surfaces and adherent platelets (hence, thrombus growth). Single-platelet and thrombus embolization were predicted from shear forces and surface adhesion strengths. Values for the platelet-biomaterial reaction constant and the platelet adhesion strength were measured in specific experiments, but all other parameter values were obtained from published sources. The model generated solutions for sequential time steps, while adjusting velocity patterns to accommodate growing surface thrombi.

Heparinized human blood was perfused (0.75 ml/min) through 580 μm-ID polyethylene flow cells with flow contractions (280 μm-ID). Thrombus initiation, growth, and embolization were observed with videomicroscopy, while embolization was confirmed by light scattering, and platelet adhesion was determined by scanning electron microscopy.

Numerical predictions and experimental observations were similar in indicating: 1) the same three thrombotic locations in the flow cell and the relative order of thrombus development in those locations, 2) equal thrombus growth rates on polyethylene and silicon rubber (in spite of differing overall T/TE), and 3) similar effects of flow rate (1.5 ml/min versus 0.75 ml/min) on platelet adhesion and thrombosis patterns.

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References

  1. Aarts, P. A. M., P. Steeniuk, J. J. Sixma, and R. M. Heethaar. Fluid shear as a possible mechanism for platelet diffusivity in flowing blood. J. Biomech. 19(10):799–805, 1986.

    Article  CAS  PubMed  Google Scholar 

  2. Adams, G. A., and I. A. Feuerstein. Platelet adhesion and release: Interfacial concentration of released materials. Am. J. Physiol. 240:H99–H108, 1981.

    CAS  PubMed  Google Scholar 

  3. Adams, G. A., and I. A. Feuerstein. Maximum fluid concentrations of materials released from platelets at a surface. Am. J. Physiol. 244:H109–H114, 1983.

    CAS  PubMed  Google Scholar 

  4. Baldwin J. T., S. Deutsch, D. B. Geselowitz, and J. M. Tarbell. Estimation of Reynolds stresses within the Penn State left ventricular assist device. ASAIO Trans. 36:M274–M278, 1990.

    CAS  PubMed  Google Scholar 

  5. Basmadjian, D. Embolization: Critical thrombus height, shear rates, and pulsatility. Patency of blood vessels. J. Biomed. Mater. Res. 23(11):1315–1326, 1989.

    Article  CAS  PubMed  Google Scholar 

  6. Basmadjian, D. The effect of flow and mass transport in thrombogenesis. Ann. Biomed. Eng. 18(6):685–709, 1990.

    CAS  PubMed  Google Scholar 

  7. Born, G. V. R. Research on the mechanism of the intravascular adhesion of circulating cells. In: Platelets and Thrombosis, edited by S. Sherry and A. Scriabin. Baltimore: University of Park Press, 1972, pp. 113–126.

  8. DeSomer F., L. Foubert, M. Vanackere, D. Dujardin, J. Delanghe, and G. Van Nooten. Impact of oxygenator design on hemolysis, shear stress, and white blood cell and platelet counts. J. Cardiothorac. Vasc. Anesth. 10(7):884–889, 1996.

    CAS  PubMed  Google Scholar 

  9. Eloot S., D. De Wachter, I. Van Tricht, and P. Verdonck. Computational flow modeling in hollow-fiber dialyzers. Artif. Org. 26(7):590–599, 2002.

    Article  Google Scholar 

  10. Feuerstein, I. A., J. M. Brophy, and J. L. Brash. Platelet transport and adhesion to reconstituted collagen and artificial surfaces. Trans. Amer. Soc. Artif. Int. Organs 21:427–435, 1975.

    CAS  Google Scholar 

  11. Feuerstein, I. A., and S. M. Buchan. Platelet adherence and detachment: A flow study with a series of hydroxyethyl methacrylate-ethyl methacrylate copolymers using video microscopy. J. Biomed. Mater. Res. 25:185–198, 1991.

    Article  CAS  PubMed  Google Scholar 

  12. Fogelson, A. L. Continuum models of platelet aggregation: Formulation and mechanical properties. J. Appl. Math. 52:1089–1110, 1992.

    Google Scholar 

  13. 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. 56(6):1121–1141, 1989.

    CAS  PubMed  Google Scholar 

  14. Frojmovic, M. M., R. F. Mooney, and T. Wong. Dynamics of platelet glycoprotein IIb-IIIa receptor expression and fibrinogen binding. I. Quantal activation of platelet subpopulations varies with adenosine diphosphate concentration. Biophys. J. 67:2060–2068, 1994.

    CAS  PubMed  Google Scholar 

  15. Frojmovic, M. M., T. Wong, and T. van de Ven. Dynamic measurements of the platelet membrane glycoprotein IIb-IIIa receptor for fibrinogen by flow cytometry. I. Methodology, theory and results for two distinct activators. Biophys. J. 59:815–827, 1991.

    CAS  PubMed  Google Scholar 

  16. Fung, Y. C. Biodynamics: Circulation. New York: Springer-Verlag, 1984.

    Google Scholar 

  17. Giacomini, A., P., Legovini, F. Antico, G. S. Gessoni, S. Valverde, M. M. Salvadego, and F. Manoni. Evaluation of platelet analysis on the ADVIA 120 Hematology System. Lab. Hematol. 7:180–185, 2001.

    CAS  Google Scholar 

  18. Goldsmith, H. L., and V. T. Turitto. Rheological aspects of thrombosis and haemostasis: Basic principles and applications. Thromb. Haemost. 55(3):415–435, 1986.

    CAS  PubMed  Google Scholar 

  19. Goodman, P. D., M. W. Hall, S. Sukavaneshvar, and K. A. Solen. In vitro model for studying the effects of hemodynamics on device induced thromboembolism in human blood. ASAIO J. 46:576–578, 2000.

    Article  CAS  PubMed  Google Scholar 

  20. Grabowski, E. F., J. T. Franta, and P. Didisheim. Platelet aggregation in flowing blood in vitro. II. Dependence of aggregate growth rate on ADP concentration and shear rate. Microvasc. Res. 16:183–195, 1978.

    Article  CAS  PubMed  Google Scholar 

  21. Grabowski, E. F., L. I. Friedman, and E. F. Leonard. Effects of shear rate on the diffusion and adhesion of blood platelets to a foreign surface. Ind. Eng. Chem. Fundam. 11(2):224–232, 1972.

    Article  CAS  Google Scholar 

  22. Griffith, M. J. Kinetics of the heparin-enhanced antithrombin III/thrombin reaction. Evidence for a template model for the mechanism of action of heparin. J. Biol. Chem. 257:7360–7365, 1982.

    CAS  PubMed  Google Scholar 

  23. Griffith, M. J. The heparin-enhanced antithrombin III/thrombin reaction is saturable with respect to both thrombin and antithrombin III. J. Biol. Chem. 257:13899–13902, 1982.

    CAS  PubMed  Google Scholar 

  24. Gu Y. J., P. W. Boonstra, R. Graaff, A. A. Rijnsburger, H. Mungroop, and W. van Oeveren. Pressure drop, shear stress, and activation of leukocytes during cardiopulmonary bypass: A comparison between hollow fiber and flat sheet membrane oxygenators. Artif. Org. 24(1):43–48, 2000.

    Google Scholar 

  25. Hellums, J. D. 1993 Whitaker Lecture: Biorheology in thrombosis research. Ann Biomed. Eng. 22(5):445–455, 1994.

    CAS  PubMed  Google Scholar 

  26. Hubbell, J. A., and L. V. McIntire. Platelet active concentration profiles near growing thrombi. Biophys. Soc. 50:937–945, 1986.

    CAS  Google Scholar 

  27. Jen, C. J., H. Li, J. Wang, H. Chen, and S. Usami. Flow-induced detachment of adherent platelets from fibrinogen-coated surface. Heart Circ. Physiol. 39:H160–H166, 1996.

    Google Scholar 

  28. Jones, R. L., N. H. Wilson, and C. G. Marr. In: Chemistry, Biochemistry, and Pharmacological Activity of Prostanoids, edited by S. M. Roberts and F. Scheinmann. Oxford: Pergamon Press, 1979, pp. 210–220.

  29. Karnovsky, M. J. A formaldehyde-glutaraldehyde fixative of high osmolarity for use in electron microscopy. J. Cell Biol. 27:137, 1965.

    Google Scholar 

  30. Kennedy, S. D., Y. Igarashi, and T. S. Kickler. Measurement of in-vitro P-selectin expression by flow cytometry. Am. J. Clin. Pathol. 107:99–104, 1997.

    CAS  PubMed  Google Scholar 

  31. Langford, E. F., R. J. Wainwright, and J. F. Martin. Platelet activation in acute myocardial infarction and unstable angina is inhibited by nitric oxide donors. Arterioscler. Thromb. 16:51–55, 1996.

    CAS  Google Scholar 

  32. Lemire P. P., J. C. McDaniel, H. G. Wood, P. E. Allaire, N. Landrot, X. Song, S. W. Day, and D. Olsen. The application of quantitative oil streaking to the HeartQuest left ventricular assist device. Artif. Org. 26(11):971–973, 2002.

    Article  CAS  Google Scholar 

  33. Mandrusov, E., J. D. Yang, N. Pfeiffer, L. Vroman, E. Puszkin, and E. F. Leonard. Kinetics of protein deposition and replacement from a shear flow. AICHE J. 44(2):233–244, 1998.

    Article  CAS  Google Scholar 

  34. McPherson, L. B., J. D. Hellums, C. P. Alfrey, and E. C. Lynch. Platelet retention in glass bead columns: Further evidence for the importance of ADP. Blood 44:411–425, 1972.

    Google Scholar 

  35. Merrill, E. W., and G. A. Pelletier. Viscosity of human blood: Transition from Newtonian to non-Newtonian. J. Appl. Physiol. 23(2):178–182, 1967.

    CAS  PubMed  Google Scholar 

  36. Reynolds, L. O., W. H. Newren, J. F. Scolio, and I. F. Miller. A model for thromboembolization on biomaterials. J. Biomater. Sci. Polymer Ed. 4(5):451–465, 1993.

    CAS  Google Scholar 

  37. Ronco C., A. Brendolan, C. Crepaldi, M. Rodighiero, and M. Scabardi. Blood and dialysate flow distributions in hollow-fiber hemodialyzers analyzed by computerized helical scanning technique. J. Am. Soc. Nephrol. 13(Suppl. 1):S53–S61, 2002.

    Article  CAS  PubMed  Google Scholar 

  38. Rosing, J., J. L. M. L. van Rijn, E. M. Bevers, G. Van Dieijen, P. Comfurius, and R. F. A. Zwaal. The role of activated human platelets in prothrombin and factor X activation. Blood 65:319–332, 1985.

    CAS  PubMed  Google Scholar 

  39. Solen K. A., S. Sukavaneshvar, Y. Zheng, B. Hanrahan, M. W. Hall, P. Goodman, B. Goodman, and S. F. Mohammad. A light scattering instrument to detect thromboemboli in blood. J. Biomed. Opt. 8:70–79,2003.

    Article  PubMed  Google Scholar 

  40. 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(4):436–448, 1999.

    Article  CAS  PubMed  Google Scholar 

  41. 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(4):449–458, 1999.

    Article  CAS  PubMed  Google Scholar 

  42. Strong, A. B. Theoretical and experimental analysis of cellular adhesion to polymer surfaces. J. Biomed. Mater. Res. 21:1039–1055, 1987.

    Article  CAS  PubMed  Google Scholar 

  43. Stubley, G. D., A. B. Strong, W. E. Hale, and D. R. Absolom. A review of mathematical models for the prediction of blood cell adhesion. Phys. Chem. Hydrodyn. 8(2):221–235, 1987.

    Google Scholar 

  44. Treichler J., S. E. Rosenow, G. Damm, K. Haito, Y. Ohara, K. Mizuguchi, K. Makinouchi, S. Takatani, and Y. Nosé. A fluid dynamic analysis of a rotary blood pump for design improvement. Artif. Org. 17(9):797–808,1993.

    Google Scholar 

  45. Tschopp, T. B. and H. R. Baumgartner. Enzymatic removal of ADP from plasma: Unaltered platelet adhesion but reduced aggregation on subendothelium and collagen fibrils. Thromb. Haemost. 35:334–341, 1976.

    CAS  PubMed  Google Scholar 

  46. Turrito, V. T., and H. R. Baumgartner. Platelet deposition on the subendothelium exposed to flowing blood: Mathematical analysis of physical parameters. Trans. Amer. Soc. Artif. Int. Organs 21:593–601, 1975.

    Google Scholar 

  47. Weiss, H. J., and W. A. Smith. Platelets: Pathophysiology and Antiplatelet Drug Therapy. New York: Liss, 1982.

    Google Scholar 

  48. Wooton, D. M., C. P. Markou, S. R. Hanson, and D. N. Ku. A mechanistic model of acute platelet accumulation in thrombogenic stenoses. Ann. Biomed. Eng. 29(4):321–329, 2001.

    Article  PubMed  Google Scholar 

  49. Wu, Y. P., P. G. de Groot, and J. J. Sixma. Shear-stress-induced detachment of blood platelets from various surfaces. Arterioscler. Thromb. Vasc. Biol. 17(11):3202–3207, 1997.

    CAS  PubMed  Google Scholar 

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Correspondence to Kenneth A. Solen Ph.D..

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Goodman, P.D., Barlow, E.T., Crapo, P.M. et al. Computational Model of Device-Induced Thrombosis and Thromboembolism. Ann Biomed Eng 33, 780–797 (2005). https://doi.org/10.1007/s10439-005-2951-z

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  • DOI: https://doi.org/10.1007/s10439-005-2951-z

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