Platelet size distribution measurements as indicators of shear stress-induced platelet aggregation

S. M. Slack, L. K. Jennings, V. T. Turitto

Research output: Contribution to journalArticlepeer-review

22 Scopus citations

Abstract

The mechanisms underlying shear stress-induced platelet aggregation (SIPA) were investigated by measuring changes in the platelet size distributions resulting from the exposure of human platelet-rich plasma (PRP) to well-defined shear stresses in a modified viscometer. Exposure of PRP to a shear stress of 100 dyne/cm2 for 1 min at 37°C resulted in the loss of single platelets, an overall shift in the distribution to larger particle sizes, and the generation of platelet fragments. Treatment of PRP prior to shearing with a monoclonal antibody directed against platelet glycoprotein (GP) IIb-IIIa (integrin αIIbβ3) at a concentration that completely inhibited ADP-induced platelet aggregation also inhibited SIPA. Furthermore, incubation of PRP with a recombinant fragment of von Willebrand factor (vWF) that abolishes ristocetin-induced platelet agglutination significantly inhibited but did not eliminate SIPA. Pretreatment of PRP with the tetrapeptides RGDS or RGDV, which constitute the GP IIb-IIIa peptide recognition sequences on fibrinogen and vWF, almost completely blocked platelet aggregation at 100 dyne/cm2, whereas the negative control peptide RGES had no discernible effect. Finally, incubation of PRP with a monoclonal antibody directed against the platelet vitronectin receptor (integrin αvβ3) did not affect SIPA. These results indicate that both GP IIb-IIIa and GP Ib, the latter through its interaction with vWF, are required for SIPA at 100 dyne/cm2; that the interaction of GP IIb-IIIa with its adhesive ligands under shear stress can be inhibited by RGD-containing peptides; and that the vitronectin receptor on platelets, which shares the same β3 subunit as GP IIb-IIIa, plays no role in SIPA. On the basis of these results, the assessment of platelet size distributions provides a sensitive and quantitative measurement for the study of SIPA.

Original languageEnglish
Pages (from-to)653-659
Number of pages7
JournalAnnals of Biomedical Engineering
Volume22
Issue number6
DOIs
StatePublished - Nov 1994
Externally publishedYes

Keywords

  • Integrins
  • Platelet aggregation
  • Shear stress
  • Viscometer

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