Skip to main content
SpringerLink
Log in

Review of Mechanical Testing and Modelling of Thrombus Material for Vascular Implant and Device Design

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

Abstract

A thrombus or blood clot is a solid mass, made up of a network of fibrin, platelets and other blood components. Blood clots can form through various pathways, for example as a result of exposed tissue factor from vascular injury, as a result of low flow/stasis, or in very high shear flow conditions. Embolization of cardiac or vascular originating blood clots, causing an occlusion of the neurovasculature, is the major cause of stroke and accounts for 85% of all stroke. With mechanical thrombectomy emerging as the new standard of care in the treatment of acute ischemic stroke (AIS), the need to generate a better understanding of the biomechanical properties and material behaviour of thrombus material has never been greater, as it could have many potential benefits for the analysis and performance of these treatment devices. Defining the material properties of a thrombus has obvious implications for the development of these treatment devices. However, to-date this definition has not been adequately established. While some experimentation has been performed, model development has been extremely limited. This paper reviews the previous literature on mechanical testing of thrombus material. It also explores the use of various constitutive and computational models to model thrombus formation and material behaviour.

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

Figure 1
Figure 2
Figure 3
Figure 4
Figure 5
Figure 6

Similar content being viewed by others

References

  1. Akbik, F., J. A. Hirsch, P. T. Cougo-Pinto, R. V. Chandra, C. Z. Simonsen, and T. Leslie-Mazwi. The evolution of mechanical thrombectomy for acute stroke. Curr. Treat. Options Cardiovasc. Med. 18:32, 2016.

    Article  PubMed  Google Scholar 

  2. Ashton, J. H., J. P. Vande Geest, B. R. Simon, and D. G. Haskett. Compressive mechanical properties of the intraluminal thrombus in abdominal aortic aneurysms and fibrin-based thrombus mimics. J. Biomech. 42:197–201, 2009.

    Article  PubMed  Google Scholar 

  3. Babushkina, E. S., N. M. Bessonov, F. I. Ataullakhanov, and M. A. Panteleev. Continuous modeling of arterial platelet thrombus formation using a spatial adsorption equation. PLoS ONE 10:e0141068, 2015.

    Article  PubMed  PubMed Central  Google Scholar 

  4. Berkhemer, O. A., et al. A randomized trial of intraarterial treatment for acute ischemic stroke. N. Engl. J. Med. 372:11–20, 2014.

    Article  PubMed  Google Scholar 

  5. Bodnár, T., and A. Sequeira. Numerical simulation of the coagulation dynamics of blood. Comput. Math. Methods Med. 9:83–104, 2008.

    Article  Google Scholar 

  6. Brown, A. E. X., R. I. Litvinov, D. E. Discher, P. K. Purohit, and J. W. Weisel. Multiscale mechanics of fibrin polymer: gel stretching with protein unfolding and loss of water. Science 325:741–744, 2009.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Burghardt, W. R., T. K. Goldstick, J. Leneschmidt, and K. Kempka. Nonlinear viscoelasticity and the thrombelastograph: 1. Studies on bovine plasma clots. Biorheology 32:621–630, 1995.

    Article  CAS  PubMed  Google Scholar 

  8. Carr, M. E., and S. L. Carr. Fibrin structure and concentration alter clot elastic modulus but do not alter platelet mediated force development. Blood Coagul. Fibrinolysis 6:79–86, 1995.

    Article  CAS  PubMed  Google Scholar 

  9. Center for Devices and Radiological Health. Guidance for Industry and FDA Staff Pre-Clinical and Clinical Studies for Neurothrombectomy Devices. 2007

  10. Center for Devices and Radiological Health. Guidance for Industry and FDA Staff—Non-Clinical Engineering Tests and Recommended Labeling for Intravascular Stents and Associated Delivery Systems. Center for Devices and Radiological Health, 2010

  11. Chandran, V. D., O. E. Kadri, and R. S. Voronov. Thrombus yield stress calculation from LBM based on intravital laser injury images in mice. In: Northeast Bioengineering Conference (NEBEC), 2017. http://nebec.njit.edu/PDFfiles/NEBEC2017-000272.pdf

  12. Chen, E. J., J. Novakofski, W. K. Jenkins, and W. D. O’Brien. Young’s modulus measurements of soft tissues with application to elasticity imaging. IEEE Trans. Ultrason. Ferroelectr. Freq. Control 43:191–194, 1996.

    Article  Google Scholar 

  13. Chueh, J. Y., A. K. Wakhloo, G. H. Hendricks, C. F. Silva, J. P. Weaver, and M. J. Gounis. Mechanical characterization of thromboemboli in acute ischemic stroke and laboratory embolus analogs. AJNR. Am. J. Neuroradiol. 32:1237–1244, 2011.

    Article  CAS  PubMed  Google Scholar 

  14. Dempfle, C.-E., T. Kälsch, E. Elmas, N. Suvajac, T. Lücke, E. Münch, and M. Borggrefe. Impact of fibrinogen concentration in severely ill patients on mechanical properties of whole blood clots. Blood Coagul. Fibrinolysis 19:765–770, 2008.

    Article  CAS  PubMed  Google Scholar 

  15. Di Martino, E., S. Mantero, F. Inzoli, G. Melissano, D. Astore, R. Chiesa, and R. Fumero. Biomechanics of abdominal aortic aneurysm in the presence of endoluminal thrombus: Experimental characterisation and structural static computational analysis. Eur. J. Vasc. Endovasc. Surg. 15:290–299, 1998.

    Article  PubMed  Google Scholar 

  16. Duffy, S., M. Farrell, K. McArdle, J. Thornton, D. Vale, E. Rainsford, L. Morris, D. S. Liebeskind, E. MacCarthy, and M. Gilvarry. Novel methodology to replicate clot analogs with diverse composition in acute ischemic stroke. J. Neurointerv. Surg. 2016. doi:10.1136/neurintsurg-2016-012308.

    Google Scholar 

  17. Fang, J., Y.-L. Wan, C.-K. Chen, and P.-H. Tsui. Discrimination between newly formed and aged thrombi using empirical mode decomposition of ultrasound B-scan image. Biomed Res. Int. 1–9:2015, 2015.

    Google Scholar 

  18. Ferry, J. D., and P. R. Morrison. Chemical, clinical, and immunological studies on the products of human plasma fractionation. XVI. fibrin clots, fibrin films, and fibrinogen plastics. J. Clin. Invest. 23:566–572, 1944.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Fogelson, A. L., and R. D. Guy. Immersed-boundary-type models of intravascular platelet aggregation. Comput. Methods Appl. Mech. Eng. 197:2087–2104, 2008.

    Article  Google Scholar 

  20. Fukada, E., Y. Sugiura, M. Date, and M. Kaibara. Methods to study rheological properties of blood during clotting. Biorheology Suppl. 1:9–14, 1984.

    CAS  PubMed  Google Scholar 

  21. Furie, B., and B. C. Furie. Mechanisms of thrombus formation. N. Engl. J. Med. 359:938–949, 2008.

    Article  CAS  PubMed  Google Scholar 

  22. Gasser, T. C., G. Görgülü, M. Folkesson, and J. Swedenborg. Failure properties of intraluminal thrombus in abdominal aortic aneurysm under static and pulsating mechanical loads. J. Vasc. Surg. 48:179–188, 2008.

    Article  PubMed  Google Scholar 

  23. Goyal, M., et al. Randomized assessment of rapid endovascular treatment of ischemic stroke. N. Engl. J. Med. 372:1019–1030, 2015.

    Article  CAS  PubMed  Google Scholar 

  24. Gralla, J., G. Schroth, L. Remonda, K. Nedeltchev, J. Slotboom, and C. Brekenfeld. Mechanical thrombectomy for acute ischemic stroke: thrombus-device interaction, efficiency, and complications in vivo. Stroke. 37:3019–3024, 2006.

    Article  PubMed  Google Scholar 

  25. Gunning, G. M., K. Mcardle, M. Mirza, S. Duffy, M. Gilvarry, and P. A. Brouwer. Clot friction variation with fibrin content; implications for resistance to thrombectomy. J. Neurointerventioal Surg. 372:1019–1030, 2016.

    Google Scholar 

  26. Hinnen, J. W., D. J. Rixen, O. H. J. Koning, J. H. van Bockel, and J. F. Hamming. Development of fibrinous thrombus analogue for in vitro abdominal aortic aneurysm studies. J. Biomech. 40:289–295, 2007.

    Article  CAS  PubMed  Google Scholar 

  27. Hrapko, M., J. A. W. van Dommelen, G. W. M. Peters, and J. S. H. M. Wismans. The mechanical behaviour of brain tissue: large strain response and constitutive modelling. Biorheology 43:623–636, 2006.

    CAS  PubMed  Google Scholar 

  28. Huang, C.-C., P.-Y. Chen, and C.-C. Shih. Estimating the viscoelastic modulus of a thrombus using an ultrasonic shear-wave approach. Med. Phys. 40:42901, 2013.

    Article  Google Scholar 

  29. Huang, C. C., Y. H. Lin, T. Y. Liu, P. Y. Lee, and S. H. Wang. Review: study of the blood coagulation by ultrasound. J. Med. Biol. Eng. 31:79–86, 2011.

    Article  CAS  Google Scholar 

  30. Humphrey, J. D., and G. A. Holzapfel. Mechanics, mechanobiology and modeling of human abdominal aorta and aneurysms. J. Biomech. 45:805–815, 2012.

    Article  CAS  PubMed  Google Scholar 

  31. Karsaj, I., and J. D. Humphrey. A mathematical model of evolving mechanical properties of intraluminal thrombus. Biorheology 46:509–527, 2009.

    CAS  PubMed  PubMed Central  Google Scholar 

  32. Kim, E., O. V. Kim, K. R. Machlus, X. Liu, T. Kupaev, J. Lioi, A. S. Wolberg, D. Z. Chen, E. D. Rosen, Z. Xu, and M. Alber. Correlation between fibrin network structure and mechanical properties: an experimental and computational analysis. Soft Matter 7:4983, 2011.

    Article  CAS  Google Scholar 

  33. Kim, O. V., R. I. Litvinov, J. W. Weisel, and M. S. Alber. Structural basis for the nonlinear mechanics of fibrin networks under compression. Biomaterials 35:6739–6749, 2014.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  34. Krasokha, N. W., S. Theisen, P. Reese, C. Mordasini, J. Brekenfeld, J. Gralla, G. Slotboom Schrott, and H. Monstadt. Mechanical properties of blood clots—a new test method. Mechanische Eigenschaften von Thromben - Neue Untersuchungsmethoden. Materwiss. Werksttech. 41:1019–1024, 2010.

    Article  CAS  Google Scholar 

  35. Liu, K., M. R. VanLandingham, and T. C. Ovaert. Mechanical characterization of soft viscoelastic gels via indentation and optimization-based inverse finite element analysis. J. Mech. Behav. Biomed. Mater 2:355–363, 2009.

    Article  PubMed  Google Scholar 

  36. Mozaffarian, D. Heart disease and stroke statistics—2016 update. Circulation 133:e38–e360, 2015.

    Article  PubMed  Google Scholar 

  37. Noailly, J., H. Van Oosterwyck, W. Wilson, T. M. Quinn, and K. Ito. A poroviscoelastic description of fibrin gels. J. Biomech. 41:3265–3269, 2008.

    Article  PubMed  Google Scholar 

  38. O’Leary, S. A., E. G. Kavanagh, P. A. Grace, T. M. McGloughlin, and B. J. Doyle. The biaxial mechanical behaviour of abdominal aortic aneurysm intraluminal thrombus: classification of morphology and the determination of layer and region specific properties. J. Biomech 47:1430–1437, 2014.

    Article  PubMed  Google Scholar 

  39. Pivkin, I. V., P. D. Richardson, and G. Karniadakis. Blood flow velocity effects and role of activation delay time on growth and form of platelet thrombi. Proc. Natl. Acad. Sci. U. S. A. 103:17164–17169, 2006.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  40. Polzer, S., T. Gasser, B. Markert, J. Bursa, and P. Skacel. Impact of poroelasticity of intraluminal thrombus on wall stress of abdominal aortic aneurysms. Biomed. Eng. Online 11:62, 2012.

    Article  PubMed  PubMed Central  Google Scholar 

  41. Robinson, R. A., L. H. Herbertson, S. Sarkar Das, R. A. Malinauskas, W. F. Pritchard, and L. W. Grossman. Limitations of using synthetic blood clots for measuring in vitro clot capture efficiency of inferior vena cava filters. Med. Devices (Auckl) 6:49–57, 2013.

    CAS  PubMed Central  Google Scholar 

  42. Ryan, E. A., L. F. Mockros, J. W. Weisel, and L. Lorand. Structural origins of fibrin clot. Rheology. 77:2813–2826, 1999.

    CAS  Google Scholar 

  43. Saldívar, E., J. N. Orje, and Z. M. Ruggeri. Tensile destruction test as an estimation of partial proteolysis in fibrin clots. Am. J. Hematol. 71:119–127, 2002.

    Article  PubMed  Google Scholar 

  44. Schmitt, C., A. Hadj Henni, and G. Cloutier. Characterization of blood clot viscoelasticity by dynamic ultrasound elastography and modeling of the rheological behavior. J. Biomech. 44:622–629, 2011.

    Article  PubMed  Google Scholar 

  45. Slaboch, C. L., M. S. Alber, E. D. Rosen, and T. C. Ovaert. Mechano-rheological properties of the murine thrombus determined via nanoindentation and finite element modeling. J. Mech. Behav. Biomed. Mater. 10:75–86, 2012.

    Article  PubMed  Google Scholar 

  46. Stary, H. Atlas of Atherosclerosis Progression and Regression. New York/London: Parthenon Publishing, 1999.

    Google Scholar 

  47. Teng, Z., J. Feng, Y. Zhang, Y. Huang, M. P. F. Sutcliffe, A. J. Brown, Z. Jing, J. H. Gillard, and Q. Lu. Layer- and direction-specific material properties, extreme extensibility and ultimate material strength of human abdominal aorta and aneurysm: a uniaxial extension study. Ann. Biomed. Eng. 43:2745–2759, 2015.

    Article  PubMed  PubMed Central  Google Scholar 

  48. van Dam, E. A., S. D. Dams, G. W. M. Peters, M. C. M. Rutten, G. W. H. Schurink, J. Buth, and F. N. van de Vosse. Determination of linear viscoelastic behavior of abdominal aortic aneurysm thrombus. Biorheology 43:695–707, 2006.

    PubMed  Google Scholar 

  49. van Dam, E. A., S. D. Dams, G. W. M. Peters, M. C. M. Rutten, G. W. H. Schurink, J. Buth, and F. N. van de Vosse. Non-linear viscoelastic behavior of abdominal aortic aneurysm thrombus. Biomechan Model Mechanobiol 7:127–137, 2008.

    Article  Google Scholar 

  50. van Kempen, T. H. S., A. C. B. Bogaerds, G. W. M. Peters, and F. N. van de Vosse. A constitutive model for a maturing fibrin network. Biophys. J. 107:504–513, 2014.

    Article  PubMed  PubMed Central  Google Scholar 

  51. van Kempen, T. H. S., W. P. Donders, F. N. van de Vosse, and G. W. M. Peters. A constitutive model for developing blood clots with various compositions and their nonlinear viscoelastic behavior. Biomech. Model. Mechanobiol. 2015. doi:10.1007/s10237-015-0686-9.

    Google Scholar 

  52. van Kempen, T. H. S., G. W. M. Peters, and F. N. van de Vosse. A constitutive model for the time-dependent, nonlinear stress response of fibrin networks. Biomech. Model. Mechanobiol. 14:995–1006, 2015.

    Article  PubMed  PubMed Central  Google Scholar 

  53. Vande Geest, J. P., M. S. Sacks, D. A. Vorp, B. Ray, G. Kuhan, I. C. Chetter, and P. T. McCollum. A planar biaxial constitutive relation for the luminal layer of intra-luminal thrombus in abdominal aortic aneurysms. J. Biomech. 39:2347–2354, 2006.

    Article  PubMed  Google Scholar 

  54. Vidmar, J., I. Serša, E. Kralj, and P. Popovič. Unsuccessful percutaneous mechanical thrombectomy in fibrin-rich high-risk pulmonary thromboembolism. Thromb. J. 13:30, 2015.

    Article  PubMed  PubMed Central  Google Scholar 

  55. Wang, D. H., M. Makaroun, M. W. Webster, and D. A. Vorp. Mechanical properties and microstructure of intraluminal thrombus from abdominal aortic aneurysm. J. Biomech. Eng. 123:536–539, 2001.

    Article  CAS  PubMed  Google Scholar 

  56. Weisel, J. W. The mechanical properties of fibrin for basic scientists and clinicians. Biophys. Chem. 112:267–276, 2004.

    Article  CAS  PubMed  Google Scholar 

  57. Weisel, J. W. Structure of fibrin: impact on clot stability. J. Thromb. Haemost. 5(Suppl 1):116–124, 2007.

    Article  CAS  PubMed  Google Scholar 

  58. Weisel, J. W. Biophysics. Enigmas of blood clot elasticity. Science 320:456–457, 2008.

    Article  CAS  PubMed  Google Scholar 

  59. Weisel, J. W. Biomechanics in haemostasis and thrombosis. J. Thromb. Haemost. 8:1027–1029, 2010.

    CAS  PubMed  Google Scholar 

  60. Xie, H., K. Kim, S. R. Aglyamov, S. Y. Emelianov, M. O’Donnell, W. F. Weitzel, S. K. Wrobleski, D. D. Myers, T. W. Wakefield, and J. M. Rubin. Correspondence of ultrasound elasticity imaging to direct mechanical measurement in aging DVT in rats. Ultrasound Med. Biol. 31:1351–1359, 2005.

    Article  PubMed  PubMed Central  Google Scholar 

  61. Xu, Z., N. Chen, M. M. Kamocka, E. D. Rosen, and M. Alber. A multiscale model of thrombus development. J. R. Soc. Interface 5:705–722, 2008.

    Article  PubMed  Google Scholar 

  62. Xu, Z., M. Kamocka, M. Alber, and E. D. Rosen. Computational approaches to studying thrombus development. Arterioscler. Thromb. Vasc. Biol. 31:500–505, 2011.

    Article  PubMed  Google Scholar 

  63. Xu, Z., O. Kim, M. Kamocka, E. D. Rosen, and M. Alber. Multiscale models of thrombogenesis. Wiley Interdiscip. Rev. Syst. Biol. Med. 4:237–246, 2012.

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgments

The authors would like to acknowledge the support of Neuravi Ltd, the Irish Research Council Enterprise Partnership Scheme and the NUI Galway Hardiman Research Scholarship for this research.

Author information

Authors and Affiliations

  1. Biomechanics Research Centre (BMEC), Biomedical Engineering, College of Engineering and Informatics, National University of Ireland, Galway, Ireland

    S. Johnson, J. P. McGarry & P. E. McHugh

  2. Galway-Mayo Institute of Technology, Galway, Ireland

    S. Duffy

  3. Neuravi Ltd, Galway, Ireland

    S. Duffy, G. Gunning & M. Gilvarry

Authors
  1. S. Johnson
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. S. Duffy
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. G. Gunning
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. M. Gilvarry
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. J. P. McGarry
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. P. E. McHugh
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to S. Johnson.

Additional information

Associate Editors K. A. Athanasiou, Editor-in-Chief oversaw the review of this article.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Johnson, S., Duffy, S., Gunning, G. et al. Review of Mechanical Testing and Modelling of Thrombus Material for Vascular Implant and Device Design. Ann Biomed Eng 45, 2494–2508 (2017). https://doi.org/10.1007/s10439-017-1906-5

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10439-017-1906-5

Keywords

Search

Navigation