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Annals of Biomedical Engineering

, Volume 38, Issue 4, pp 1442–1450 | Cite as

High-Shear Stress Sensitizes Platelets to Subsequent Low-Shear Conditions

  • Jawaad Sheriff
  • Danny Bluestein
  • Gaurav Girdhar
  • Jolyon JestyEmail author
Article

Abstract

Individuals with mechanical heart valve implants are plagued by flow-induced thromboembolic complications, which are undoubtedly caused by platelet activation. Flow fields in or around the affected regions involve brief exposure to pathologically high-shear stresses on the order of 100 to 1000 dyne/cm2. Although high shear is known to activate platelets directly, their subsequent behavior is not known. We hypothesize that the post-high-shear activation behavior of platelets is particularly relevant in understanding the increased thrombotic risk associated with blood-recirculating prosthetic cardiovascular devices. Purified platelets were exposed to brief (5–40 s) periods of high-shear stress, and then exposed to longer periods (15–60 min) of low shear. Their activation state was measured using a prothrombinase-based assay. Platelets briefly exposed to an initial high-shear stress (e.g., 60 dyne/cm2 for 40 s) activate a little, but this study shows that they are now sensitized, and when exposed to subsequent low shear stress, they activate at least 20-fold faster than platelets not initially exposed to high shear. The results show that platelets in vitro exposed beyond a threshold of high-shear stress are primed for subsequent activation under normal cardiovascular circulation conditions, and they do not recover from the initial high-shear insult.

Keywords

Thrombosis Hemodynamics Shear-induced platelet activation 

Notes

Acknowledgments

The authors would like to thank Philip Chiu, Mohammed Hoque, and Thomas Claiborne for their contributions to the experiments in this study. This study was supported by the American Heart Association (Award no. 0340143N, DB) and the National Institutes of Health (Award no. 1R01EB008004-01, DB).

References

  1. 1.
    Akins, C. W. Results with mechanical cardiac valvular prostheses. Ann. Thorac. Surg. 60:1836–1844, 1995.CrossRefPubMedGoogle Scholar
  2. 2.
    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.CrossRefPubMedGoogle Scholar
  3. 3.
    Aursnes, I., J. Sundal, and T. Nome. Shear stress activation of platelets with subsequent refractoriness. Thromb. Res. 45:29–37, 1987.CrossRefPubMedGoogle Scholar
  4. 4.
    Bahou, W. F., L. Scudder, D. Rubenstein, and J. Jesty. A shear-restricted pathway of platelet procoagulant activity is regulated by IQGAP1. J. Biol. Chem. 279:22571–22577, 2004.CrossRefPubMedGoogle Scholar
  5. 5.
    Bluestein, D. Towards optimization of the thrombogenic potential of blood recirculating cardiovascular devices using modeling approaches. Expert. Rev. Med. Devices 3:267–270, 2006.CrossRefPubMedGoogle Scholar
  6. 6.
    Bluestein, D., W. Yin, K. Affeld, and J. Jesty. Flow-induced platelet activation in mechanical heart valves. J. Heart Valve Dis. 13:501–508, 2004.PubMedGoogle Scholar
  7. 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. 8.
    Bray, P. F. Platelet hyperreactivity: predictive and intrinsic properties. Hematol. Oncol. Clin. North Am. 21:633–645, v–vi, 2007.Google Scholar
  9. 9.
    Brown, III, 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. Intern. Organs 21:35–39, 1975.PubMedGoogle Scholar
  10. 10.
    Butchart, E. G., A. Ionescu, N. Payne, J. Giddings, G. L. Grunkemeier, and A. G. Fraser. A new scoring system to determine thromboembolic risk after heart valve replacement. Circulation 108(Suppl 1):II68–II74, 2003.Google Scholar
  11. 11.
    Butchart, E. G., P. A. Lewis, G. L. Grunkemeier, N. Kulatilake, and I. M. Breckenridge. Low risk of thrombosis and serious embolic events despite low-intensity anticoagulation. Experience with 1,004 Medtronic Hall valves. Circulation 78:I66–I77, 1988.PubMedGoogle Scholar
  12. 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. Intern. Organs 23:626–631, 1977.PubMedGoogle Scholar
  13. 13.
    Davies, T. A., D. L. Drotts, G. J. Weil, and E. R. Simons. Cytoplasmic Ca2+ is necessary for thrombin-induced platelet activation. J. Biol. Chem. 264:19600–19606, 1989.PubMedGoogle Scholar
  14. 14.
    Edmunds, Jr., L. H. Thrombotic and bleeding complications of prosthetic heart valves. Ann. Thorac. Surg. 44:430–445, 1987.PubMedCrossRefGoogle Scholar
  15. 15.
    Goldsmith, H. L., and V. T. Turitto. Rheological aspects of thrombosis and haemostasis: basic principles and applications. ICTH Report—Subcommittee on Rheology of the International Committee on Thrombosis and Haemostasis. Thromb. Haemost. 55:415–435, 1986.PubMedGoogle Scholar
  16. 16.
    Grigioni, M., C. Daniele, G. D’Avenio, and V. Barbaro. A discussion on the threshold limit for hemolysis related to Reynolds shear stress. J. Biomech. 32:1107–1112, 1999.CrossRefPubMedGoogle Scholar
  17. 17.
    Hathcock, J. J. Flow effects on coagulation and thrombosis. Arterioscler. Thromb. Vasc. Biol. 26:1729–1737, 2006.CrossRefPubMedGoogle Scholar
  18. 18.
    Jesty, J., and D. Bluestein. Acetylated prothrombin as a substrate in the measurement of the procoagulant activity of platelets: elimination of the feedback activation of platelets by thrombin. Anal. Biochem. 272:64–70, 1999.CrossRefPubMedGoogle Scholar
  19. 19.
    Jesty, J., W. Yin, P. Perrotta, and D. Bluestein. Platelet activation in a circulating flow loop: combined effects of shear stress and exposure time. Platelets 14:143–149, 2003.CrossRefPubMedGoogle Scholar
  20. 20.
    Kottke-Marchant, K. Importance of platelets and platelet response in acute coronary syndromes. Cleve. Clin. J. Med. 76(Suppl 1):S2–S7, 2009.CrossRefPubMedGoogle Scholar
  21. 21.
    Kroll, M. H., J. D. Hellums, L. V. McIntire, A. I. Schafer, and J. L. Moake. Platelets and shear stress. Blood 88:1525–1541, 1996.PubMedGoogle Scholar
  22. 22.
    Leytin, V., D. J. Allen, S. Mykhaylov, L. Mis, E. V. Lyubimov, B. Garvey, and J. Freedman. Pathologic high shear stress induces apoptosis events in human platelets. Biochem. Biophys. Res. Commun. 320:303–310, 2004.CrossRefPubMedGoogle Scholar
  23. 23.
    Miyazaki, Y., S. Nomura, T. Miyake, H. Kagawa, C. Kitada, H. Taniguchi, Y. Komiyama, Y. Fujimura, Y. Ikeda, and S. Fukuhara. High shear stress can initiate both platelet aggregation and shedding of procoagulant containing microparticles. Blood 88:3456–3464, 1996.PubMedGoogle Scholar
  24. 24.
    Nobili, M., J. Sheriff, U. Morbiducci, A. Redaelli, and D. Bluestein. Platelet activation due to hemodynamic shear stresses: damage accumulation model and comparison to in vitro measurements. ASAIO J. 54:64–72, 2008.CrossRefPubMedGoogle Scholar
  25. 25.
    Nomura, S. Function and clinical significance of platelet-derived microparticles. Int. J. Hematol. 74:397–404, 2001.CrossRefPubMedGoogle Scholar
  26. 26.
    Piccin, A., W. G. Murphy, and O. P. Smith. Circulating microparticles: pathophysiology and clinical implications. Blood Rev. 21:157–171, 2007.CrossRefPubMedGoogle Scholar
  27. 27.
    Ramstack, J. M., L. Zuckerman, and L. F. Mockros. Shear-induced activation of platelets. J. Biomech. 12:113–125, 1979.CrossRefPubMedGoogle Scholar
  28. 28.
    Schulz-Heik, K., J. Ramachandran, D. Bluestein, and J. Jesty. The extent of platelet activation under shear depends on platelet count: differential expression of anionic phospholipid and factor Va. Pathophysiol. Haemost. Thromb. 34:255–262, 2005.CrossRefPubMedGoogle Scholar
  29. 29.
    Shankaran, H., P. Alexandridis, and S. Neelamegham. Aspects of hydrodynamic shear regulating shear-induced platelet activation and self-association of von Willebrand factor in suspension. Blood 101:2637–2645, 2003.CrossRefPubMedGoogle Scholar
  30. 30.
    Sutera, S. P., and M. H. Mehrjardi. Deformation and fragmentation of human red blood cells in turbulent shear flow. Biophys. J. 15:1–10, 1975.CrossRefPubMedGoogle Scholar
  31. 31.
    Travis, B. R., U. M. Marzec, H. L. Leo, T. Momin, C. Sanders, S. R. Hanson, and A. P. Yoganathan. Bileaflet aortic valve prosthesis pivot geometry influences platelet secretion and anionic phospholipid exposure. Ann. Biomed. Eng. 29:657–664, 2001.CrossRefPubMedGoogle Scholar
  32. 32.
    Voisin, P., C. Guimont, and J. F. Stoltz. Experimental investigation of the rheological activation of blood platelets. Biorheology 22:425–435, 1985.PubMedGoogle Scholar
  33. 33.
    Wootton, D. M., and D. N. Ku. Fluid mechanics of vascular systems, diseases, and thrombosis. Annu. Rev. Biomed. Eng. 1:299–329, 1999.CrossRefPubMedGoogle Scholar
  34. 34.
    Wurzinger, L. J., R. Opitz, P. Blasberg, and H. Schmid-Schonbein. Platelet and coagulation parameters following millisecond exposure to laminar shear stress. Thromb. Haemost. 54:381–386, 1985.PubMedGoogle Scholar
  35. 35.
    Yee, D. L., A. L. Bergeron, C. W. Sun, J. F. Dong, and P. F. Bray. Platelet hyperreactivity generalizes to multiple forms of stimulation. J. Thromb. Haemost. 4:2043–2050, 2006.CrossRefPubMedGoogle Scholar
  36. 36.
    Yee, D. L., C. W. Sun, A. L. Bergeron, J. F. Dong, and P. F. Bray. Aggregometry detects platelet hyperreactivity in healthy individuals. Blood 106:2723–2729, 2005.CrossRefPubMedGoogle Scholar
  37. 37.
    Yin, W., S. Gallocher, L. Pinchuk, R. T. Schoephoerster, J. Jesty, and D. Bluestein. Flow-induced platelet activation in a St. Jude mechanical heart valve, a trileaflet polymeric heart valve, and a St. Jude tissue valve. Artif. Organs 29:826–831, 2005.CrossRefPubMedGoogle Scholar
  38. 38.
    Yoganathan, A. P., Z. He, and S. Casey Jones. Fluid mechanics of heart valves. Annu. Rev. Biomed. Eng. 6:331–362, 2004.CrossRefPubMedGoogle Scholar
  39. 39.
    Zhang, J. N., A. L. Bergeron, Q. Yu, C. Sun, L. McBride, P. F. Bray, and J. F. Dong. Duration of exposure to high fluid shear stress is critical in shear-induced platelet activation-aggregation. Thromb. Haemost. 90:672–678, 2003.PubMedGoogle Scholar
  40. 40.
    Zhang, J. N., A. L. Bergeron, Q. Yu, C. Sun, L. V. McIntire, J. A. Lopez, and J. F. Dong. Platelet aggregation and activation under complex patterns of shear stress. Thromb. Haemost. 88:817–821, 2002.PubMedGoogle Scholar

Copyright information

© Biomedical Engineering Society 2010

Authors and Affiliations

  • Jawaad Sheriff
    • 1
  • Danny Bluestein
    • 1
  • Gaurav Girdhar
    • 1
  • Jolyon Jesty
    • 2
    Email author
  1. 1.Department of Biomedical Engineering, T18-030 Health Sciences CenterStony Brook UniversityStony BrookUSA
  2. 2.Division of Hematology/Oncology, T15-040 Health Sciences Center, School of MedicineStony Brook UniversityStony BrookUSA

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