Molecular and Cellular Biochemistry

, Volume 409, Issue 1–2, pp 93–101 | Cite as

Activation and shedding of platelet glycoprotein IIb/IIIa under non-physiological shear stress

  • Zengsheng Chen
  • Nandan K. Mondal
  • Jun Ding
  • Steven C. Koenig
  • Mark S. Slaughter
  • Bartley P. Griffith
  • Zhongjun J. Wu


The purpose of this study was to investigate the influence of non-physiological high shear stress on activation and shedding of platelet GP IIb/IIIa receptors. The healthy donor blood was exposed to three levels of high shear stresses (25, 75, 125 Pa) from the physiological to non-physiological status with three short exposure time (0.05, 0.5, 1.5 s), created by a specific blood shearing system. The activation and shedding of the platelet GPIIb/IIIa were analyzed using flow cytometry and enzyme-linked immunosorbent assay. In addition, platelet P-selectin expression of sheared blood, which is a marker for activated platelets, was also analyzed. The results from the present study showed that the number of activated platelets, as indicated by the surface GPIIb/IIIa activation and P-selectin expression, increased with increasing the shear stress level and exposure time. However, the mean fluorescence of GPIIb/IIIa on the platelet surface, decreased with increasing the shear stress level and exposure time. The reduction of GPIIb/IIIa on the platelet surface was further proved by the reduction of further activated platelet GPIIb/IIIa surface expression induced by ADP and the increase in GPIIb/IIIa concentration in microparticle-free plasma with increasing the applied shear stress and exposure time. It is clear that non-physiological shear stress induce a paradoxical phenomenon, in which both activation and shedding of the GPIIb/IIIa on the platelet surface occur simultaneously. This study may offer a new perspective to explain the reason of both increased thrombosis and bleeding events in patients implanted with high shear blood-contacting medical devices.


Glycoprotein IIb/IIIa (Integrin αIIb3Blood-contacting medical devices Non-physiological shear stress Shear-induced hemostatic dysfunction Shear-induced platelet activation 



This work was partially supported by the National Institutes of Health (Grant numbers: R01 HL 088100, R01 HL124170) and the International Postdoctoral Exchange Fellowship Program (No. 20130028).

Compliance with Ethical Standards

Conflict of interest

The authors declared that there are no conflicts of interests.


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Copyright information

© Springer Science+Business Media New York 2015

Authors and Affiliations

  • Zengsheng Chen
    • 1
    • 2
  • Nandan K. Mondal
    • 1
  • Jun Ding
    • 1
    • 3
  • Steven C. Koenig
    • 1
  • Mark S. Slaughter
    • 1
  • Bartley P. Griffith
    • 4
  • Zhongjun J. Wu
    • 1
  1. 1.Department of Cardiovascular and Thoracic Surgery, Cardiovascular Innovation InstituteUniversity of Louisville School of MedicineLouisvilleUSA
  2. 2.Department of Engineering Mechanics, School of AerospaceTsinghua UniversityBeijingChina
  3. 3.Department of Mechanical EngineeringUniversity of Maryland Baltimore CountyBaltimoreUSA
  4. 4.Department of Surgery, School of MedicineUniversity of MarylandBaltimoreUSA

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