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

Mol Cell Biochem. 2015 Nov;409(1-2):93-101. doi: 10.1007/s11010-015-2515-y. Epub 2015 Jul 10.


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.

Keywords: Blood-contacting medical devices; Glycoprotein IIb/IIIa (Integrin αIIb/β3); Non-physiological shear stress; Shear-induced hemostatic dysfunction; Shear-induced platelet activation.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Blood Coagulation
  • Blood Platelets / pathology*
  • Enzyme-Linked Immunosorbent Assay
  • Female
  • Flow Cytometry
  • Hemorrhage / pathology
  • Humans
  • Male
  • P-Selectin / metabolism
  • Platelet Activation / physiology
  • Platelet Aggregation / physiology
  • Platelet Glycoprotein GPIIb-IIIa Complex / metabolism*
  • Prostheses and Implants / adverse effects*
  • Stress, Mechanical*
  • Stress, Physiological / physiology*
  • Thrombosis / pathology


  • P-Selectin
  • Platelet Glycoprotein GPIIb-IIIa Complex