Skip to main content
Log in

1993 Whitaker lecture: Biorheology in thrombosis research

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

Abstract

A review is presented on biorheological studies of platelet activation and platelet-platelet binding events that play key roles in thrombosis and hemostasis. Rheological methods have been used by a number of workers to establish the importance of fluid mechanical shear stress as a determinate of platelet reactions. Fluid mechanical shear stress can be regarded as a platelet agonist that is always present in the circulation and that is synergistic in its actions with other agonists. Early biorheological studies were phenomenological in that they focused on stress effects on measures of platelet function. Subsequent studies have elucidated mechanisms and have shown that the biochemical pathways of platelet activation are very different at elevated shear stresses than in the low shear stress environment used in many platelet activation studies. This finding that biochemical pathways of platelet activations are different at different shear stress levels suggests that it may be possible to develop platelet inhibitors of highly specific action: it may be possible to inhibit pathways important in thrombosis in a partially occluded artery without seriously compromising the normal hemostatic function of platelets. Another aspect of the work suggests that the biorheological approach may make it possible to develop better methods for prediction of thrombotic tendencies in human subjects.

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

Access this article

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

Instant access to the full article PDF.

Similar content being viewed by others

References

  1. Alkhamis, T. M., R. L. Beissinger, and J. Chedian. Effect of red blood cells on platelet adhesion and aggregation in low-stress shear flow.Trans. Am. Soc. Artif. Intern. Org. XXXIII:636–642, 1987.

    Google Scholar 

  2. Alkhamis, T. M., R. L. Beissinger, and J. Chedian. Artificial surface effect on red blood cells and platelets in laminar shear flow.Blood 75:1568–1575, 1990.

    CAS  PubMed  Google Scholar 

  3. Anderson, G. H., J. D. Hellums, J. L. Moake and C. P. Alfrey, Jr. Platelet lysis and aggregation in shear fields.Blood Cells 4:499–507, 1978.

    CAS  PubMed  Google Scholar 

  4. Anderson, G. H., J. D. Hellums, J. Moake, and C. P. Alfrey, Jr. Platelet response to shear stress: changes in serotonin uptake, serotonin release, and ADP induced aggregation.Thromb. Res. 13:1039–1047, 1978.

    Article  CAS  PubMed  Google Scholar 

  5. Bell, D. N., S. Spain, and H. L. Goldsmith. The ADP-induced aggregation of human platelet in flow through tubes. I. Measurement of the concentration and size of single platelets and aggregates.Biophys. J. 56:817–828, 1989.

    CAS  PubMed  Google Scholar 

  6. Belval, T. K., and J. D. Hellums. Analysis of shear-induced platelet aggregation with population balance mathematics.Biophys. J. 50:479–487, 1986.

    CAS  PubMed  Google Scholar 

  7. Belval, T. K., J. D. Hellums, and R. T. Solis. The kinetics of platelet aggregation induced by shear stress.Microvasc. Res. 28:279–288, 1984.

    Article  CAS  PubMed  Google Scholar 

  8. Born, G. V. R. Aggregation of blood platelets by adenosine diphosphate and its reversal.Nature 194:927–934, 1962.

    CAS  PubMed  Google Scholar 

  9. Brown, C. H., L. B. Leverett, C. W. Lewis, C. P. Alfrey, and J. D. Hellums. Morphological, biochemical and functional changes in human platelets subjected to shear stress.J. Lab. Clin. Med. 86:462–471, 1975.

    PubMed  Google Scholar 

  10. Brown, C. H. R. F. Lemuth, J. D. Hellums, L. B. Leverett, and C. P. Alfrey. Response of human platelets to shear stress.Trans. Am. Soc. Artif. Int. Org. 21:35–39, 1975.

    CAS  Google Scholar 

  11. Chow, T. W., J. D. Hellums, J. L. Moake, and M. H. Kroll. Shear stress-induced von Willebrand factor binding to platelet glycoprotein Ib initiates calcium influx associated with aggregation.Blood 80:113–120, 1992.

    CAS  PubMed  Google Scholar 

  12. Colantuoni, G., J. D. Hellums, J. L. Moake, and C. P. Alfrey, Jr. The response of human platelets to shear stress at short exposure times.Trans. Am. Soc. Artif. Int. Org. XXIII:626–630, 1977.

    Google Scholar 

  13. Coller, B. S., E. I. Peerschke L. E. Scudder, and C. A. Sullivan. Studies with a murine monoclonal antibody that abolishes ristocetin-induced binding of von Willebrand factor to platelets: additional evidence in support of GPIb as a platelet receptor for von Willebrand factor.Blood 61:99–110, 1983.

    CAS  PubMed  Google Scholar 

  14. Dewitz, T. S., R. R. Martin, R. T. Solis, J. D. Hellums, and L. V. McIntire. Stress induced platelet aggregation-microaggregate formation in whole blood exposed to shear stress.Microvasc. Res. 16:263–271, 1978.

    Article  CAS  PubMed  Google Scholar 

  15. Frojmovic, M., T. Wong, and T. Van de Ven. Dynamic measurements of the platelet membrane glycoprotein IIb-IIa 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. Fukuyama, M., K. Sakai, I. Itagaki, K. Kawano, M. Murata, Y. Kawai, K. Watanabe, M. Handa, and Y. Ikeda. Continuous measurement of shear-induced platelet aggregation.Thromb. Res. 54:253–260, 1989.

    Article  CAS  PubMed  Google Scholar 

  17. Goldsmith, H. L., J. C. Marlow, and S. K. Yu. The effect of oscillatory flow on the release reaction and aggregation of platelets.Microvasc. Res. 11:355–362, 1976.

    Article  Google Scholar 

  18. Giorgio, T. D., and J. D. Hellums. A cone and plate viscometer for the continuous measurement of blood platelet activation.Biorheology 25:605–624, 1988.

    CAS  PubMed  Google Scholar 

  19. Hardwick, R. A., J. D. Hellums, J. L. Moake, and D. M. Peterson. Effects of antiplatelet agents on platelets exposed to shear stress.Trans. Am. Soc. Artif. Int. Org. XXVI:179–184, 1980.

    Google Scholar 

  20. Hardwick, R. A., J. D. Hellums, D. M. Peterson, and J. L. Moake. The effects of ASA, PGE1, PGI2, and theophylline, on the response of platelets subjected to shear stress.Blood 58:678–681, 1981.

    CAS  PubMed  Google Scholar 

  21. Hellums, J. D., and R. A. Hardwick. Response of platelets to shear stress—a review. In: Hemovascular Rheology: The Physics of Blood and Vascular Tissue, edited by N. H. C. Hwang and D. R. Gross. Amsterdam: Sijthoff and Noorhoff, 1981, pp. 160–183.

    Google Scholar 

  22. Hellums, J. D., D. M. Peterson, N. A. Stathopoulos, J. L. Moake, and T. D. Giorgio. Studies on the mechanisms of shear-induced platelet activation. In: Cerebral Ischemia and Hemorheology, edited by A. Hartman and W. Kuschinsky. New York: Springer Verlag, 1987, pp. 80–89.

    Google Scholar 

  23. Hoogendijk, E. M., C. S. P. Jenkins, E. M. van Wijk, J. Vos, and J. W. Ten Cate. Spontaneous platelet aggregation in cerebrovascular disease. II. Further characterization of the platelet defect.Thromb. Haem. 41:512–522, 1979.

    CAS  Google Scholar 

  24. Huang, P. Y., and J. D. Hellums. Aggregation and disaggregation kinetics of human blood platelets. Part I. Development and validation of a population balance method.Biophys. J. 65:334–343, 1993.

    CAS  PubMed  Google Scholar 

  25. Huang, P. Y., and J. D. Hellums. Aggregation and disaggregation kinetics of human blood platelets. Part II. Development and validation of a population balance method.Biophys. J. 65:344–353, 1993.

    CAS  PubMed  Google Scholar 

  26. Huang, P. Y., and J. D. Hellums. Aggregation and disaggregation kinetics of human blood platelets. Part III. Development and validation of a population balance method.Biophys. J. 65:354–361, 1993.

    CAS  PubMed  Google Scholar 

  27. Hung, T. C., R. M. Hochmuth, J. H. Joist, and S. P. Sutera. Shear-induced aggregation and lysis of platelts.Trans. Am. Soc. Artif. Int. Org. XII:285–291, 1976.

    Google Scholar 

  28. Ikeda, Y., M. Handa, K. Kawano, T. Kamata, M. Murata, Y. Araki, H. Anbo, Y. Kawai, K. Watanabe, I. Itagaki, K. Sakai, and Z. M. Ruggeri. The role of von Willebrand factor and fibrinogen in platelet aggregation under varying shear stress.J. Clin. Invest. 87:1234–1240, 1991.

    CAS  PubMed  Google Scholar 

  29. Ikeda, Y., M. Murata, Y. Araki, K. Watanabe, Y. Ando, I. Itagaki, Y. Mori, M. Ichitani, and K. Sakal. Importance of fibrinogen and platelet membrane glycoprotein IIb/IIIa in shear-induced platlet aggregation.Thromb. Res. 51:157–163, 1988.

    Article  CAS  PubMed  Google Scholar 

  30. Jen, C. J., and L. V. McIntire. Characteristics of shear-induced aggregation in whole blood.J. Lab. Clin. Med. 103:115–124, 1984.

    CAS  PubMed  Google Scholar 

  31. Johnston, G. G., U. Marzek, and E. F. Bernstein. Effects of surface injury and shear stress on platelet aggregation and serotonin release.Trans. Am. Soc. Artif. Int. Org. 21:413, 1975.

    CAS  Google Scholar 

  32. Klose, H. J., H. Rieger, and H. Schmid-Schonbien. A rheological method for the quantification of platelet aggregation (PA)in vitro and its kinetics under defined flow conditions.Thromb. Res. 7:261–272, 1975.

    Article  CAS  PubMed  Google Scholar 

  33. Kroll, M. H., J. D. Hellums, Z. Guo, W. Durante, J. K. Hrbolich, and A. I. Schafer. Protein kinase C is activated in platelets subjected to pathological shear stress.J. Biol. Chem. 268:3520–3524, 1993.

    CAS  PubMed  Google Scholar 

  34. Moake, J. L., N. A. Turner, N. A., Stathopoulos, L. H. Nolasco, and J. D. Hellums. Involvement of large plasma von Willebrand factor (vWF) multimers and unusually large vWF forms derived from endothelial cells in shear stress-induced platelet aggregation.J. Clin. Invest. 78:1456–1461, 1986.

    CAS  PubMed  Google Scholar 

  35. Moake, J. L., N. A. Turner, N. A. Stathopoulos, L. Nolasco, and J. D. Hellums. Shear-induced platelet aggregation can be mediated by vWF released from platelets, as well as by exogenous large or unusually large vWF multimers, requires adenosine diphosphate, and is resistant to aspirin.Blood 71:1366–1374, 1988.

    CAS  PubMed  Google Scholar 

  36. Moritz, M. W., S. P. Sutera, and J. H. Joist. Factors influencing shear-induced platelet alterations: platelet lysis is independent of platelet aggregation and release.Thromb. Res. 22:445–455, 1981.

    Article  CAS  PubMed  Google Scholar 

  37. Moritz, M. W., R. C. Reimers, R. K. Baker, S. P. Sutera, and J. H. Joist. Tole cytoplasmic and releasable ADP in platelet aggregation induced by laminar shear stress.J. Lab. Clin. Med. 101:537–544, 1983.

    CAS  PubMed  Google Scholar 

  38. Murata, M., Y. Ikeda, Y. Araki, H. Murakami, K. Sata, M. Yamamoto, K. Watanabe, Y. Ando, T. Igawa, and I. Maruyama. Inhibition by endothelial cells of platelet aggregating activity of thrombin-role of thrombomodulin.Thromb. Res. 50:647–656, 1988.

    Article  CAS  PubMed  Google Scholar 

  39. Peterson, D. M. N. A. Stathopoulos, J. D. Hellums, and J. L. Moake. Shear-induced platelet aggregation requires von Willebrand factor and platelet membrane glycoproteins Ib and IIb-IIIa.Blood 69:625–628, 1987.

    CAS  PubMed  Google Scholar 

  40. Phillips, M. D., J. L. Moake, L. H. Nolasco, and N. A. Turner.Aurin tricarboxylic acid: a novel inhibitor of platelet-von Willebrand factor association.Blood 72:1898–1906, 1988.

    CAS  PubMed  Google Scholar 

  41. Rajagopalan, S., L. V. McIntire, E. R. Hall, and K. K. Wu. The stimulation of arachidonic acid metabolism in human platelets by hydrodynamic stresses.Biochim. Biophys. Acta 958:108–115, 1988.

    CAS  PubMed  Google Scholar 

  42. Ramstack, J. M., L. Zuckerman, and L. F. Mockros. Shear-induced activation of platelets.J. Biomech. 12:113–125, 1978.

    Google Scholar 

  43. Reimers, R. C., S. P. Sutera, and J. H. Joist. Potentiation by red blood cells of shear-induced platelet aggregation: relative importance of chemical and physical mechanisms.Blood 64:1200–1206, 1984.

    CAS  PubMed  Google Scholar 

  44. Roschke, E. J., and E. C. Harrison. Fluid shear stress in prosthetic heart valves.J. Biomech. 10:299–311, 1977.

    Article  CAS  PubMed  Google Scholar 

  45. Shattil, S. J., M. Cunningham, and J. A. Hoxie. Detection of activated platelets in whole blood using activation-dependent monoclonal antibodies and flow cytometry.Blood 70:307–315, 1987.

    CAS  PubMed  Google Scholar 

  46. Stevens, D. E., J. H. Joist, and S. P. Sutera. Role of platelet-prostaglandin synthesis in shear-induced platelet alterations.Blood 56:753–758, 1980.

    CAS  PubMed  Google Scholar 

  47. Strony, J., M. Phillips, D. Brands, J. L. Moake, and B. Adelman. Aurin tricarboxylic acid in a canine model of coronary artery thrombosis.Circulation 81:1106–1114, 1990.

    CAS  PubMed  Google Scholar 

  48. Sutera, S. P., M. D. Nowak, J. H. Joist, D. J. Zeffren, and J. E. Bauman. A programmable, computer-controlled coneplate viscometer for the application of pulsatile shear stress to platelet suspensions.Biorheology 25:449–459, 1988.

    CAS  PubMed  Google Scholar 

  49. Ten Cate, J. W., J. Vos, H. Oosterhuis, D. Prenger, and C. S. P. Jenkins. Spontaneous platelet aggregation in cerebrovascular disease.Thromb. Haem. 39:223–229, 1978.

    CAS  Google Scholar 

  50. Tiederman, W. G., M. J. Steinley, W. M. Phillips, and R. M. Privette. Turbulent shear stress from prosthetic heart valves.Trans. Am. Soc. Artif. Int. Org. 31:479–482, 1985.

    CAS  Google Scholar 

  51. Trip, M. D., V. M. Cats, F. J. L. van Capelle, and J. Vreeken. Platelet hyperreactivity and prognosis in survivors of myocardial.New Engl. J. Med. 322:1449–1454, 1990.

    Google Scholar 

  52. Voisin, P., C. Guimont, and J. F. Stoltz. Experimental investigation of the rheological activation of blood platelets.Biorheology 22:425–435, 1985.

    CAS  PubMed  Google Scholar 

  53. Weiss, H. J., J. Hawiger, Z. M. Ruggeri, V. T. Turitto, P. Thiagarajan, and T. Hoffmann. Fibrinogen-independent platelet adhesion and thrombus formation on subendothelium mediated by glycoprotein IIb-IIIa complex at high shear rate.J. Clin. Invest. 83:288–297, 1989.

    CAS  PubMed  Google Scholar 

  54. Wurzinger, L. J., R. Opitz, P. Blasberg, and H. Schmid-Schonbein. Platelet and coagulation parameters following millisecond exposure to laminal shear stress.Thromb. Haem. 54:381–386, 1985.

    CAS  Google Scholar 

  55. Wurzinger, L. J., R. Opitz, M. Wolf, and H. Schmid-Schonbein. Shear induced platelet activation—a critical reappraisal.Biorheology 22:399–413, 1985.

    CAS  PubMed  Google Scholar 

  56. Wu, K. K., and J. C. Hoak. A new method for the quantitative detection of pH. Aggregates in patients with arterial insufficiency.Lancet 2:924–926, 1974.

    CAS  PubMed  Google Scholar 

  57. Wu, K. K., and J. C. Hoak. Spontaneous platelet aggregation in arterial insufficiency: mechanism and implications.Thromb. Haem. 35:702–711, 1976.

    CAS  Google Scholar 

  58. Wu, K. K., Platelet hyperaggregability and thrombosis in patients with thrombocythemia.Ann. Int. Med. 88:7–11, 1978.

    CAS  PubMed  Google Scholar 

  59. Yung, Y., and M. Frojmovic. Platelet aggregation in laminar flow. Part I: adenosine diphosphate concentration, time, and shear rate dependence.Thromb. Res. 28:361–378, 1982.

    CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Rights and permissions

Reprints and permissions

About this article

Cite this article

Hellums, J.D. 1993 Whitaker lecture: Biorheology in thrombosis research. Ann Biomed Eng 22, 445–455 (1994). https://doi.org/10.1007/BF02367081

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF02367081

Keywords

Navigation