New strategy of platelet substitutes for enhancing platelet aggregation at high shear rates

Cooperative effects of a mixed system of fibrinogen γ-chain dodecapeptide- or glycoprotein Ibα-conjugated latex beads under flow conditions

Yosuke Okamura, Makoto Handa, Hidenori Suzuki, Yasuo Ikeda, Shinji Takeoka

Research output: Contribution to journalArticle

26 Citations (Scopus)

Abstract

To construct platelet substitutes that have hemostatic properties over a wide range of shear rates, we used fibrinogen γ-chain carboxy-terminal sequence HHLGGAKQAGDV (H12), which recognizes activated platelets at low shear rates, and a recombinant water-soluble moiety of the platelet glycoprotein (rGPIbα), which recognizes von Willebrand factor at high shear rates. Three kinds of samples were prepared for this purpose: H12-conjugated latex beads (H12-latex beads), rGPIbα-latex beads, and H12/rGPIbα-latex beads. These samples were evaluated in thrombocytopenia-imitation blood at various flow conditions. Based on ADP-induced platelet aggregation studies, the H12-latex beads significantly enhanced platelet aggregation via H12 binding with GPIIb/IIIa activated on the surface of activated platelets, whereas the rGPIbα-latex beads did not support platelet aggregation. In the case of the H12/rGPIbα-latex beads, the function of H12 was suppressed by steric hindrance from the larger rGPIbα bound to the latex bead. A mixture of the H12-latex beads and the rGPIbα-latex beads adhered to a collagen surface over a wide range of shear rates. In particular, at high shear rates, a cooperative effect was observed in the enhancement of platelet thrombus formation compared with H12-latex beads or rGPIbα-latex beads alone. We propose that a mixed system of H12- and rGPIbα-conjugated nanoparticles is a more effective platelet substitute than each of the beads used alone and has enhanced platelet aggregation properties.

Original languageEnglish
Pages (from-to)251-258
Number of pages8
JournalJournal of Artificial Organs
Volume9
Issue number4
DOIs
Publication statusPublished - 2006 Dec

Fingerprint

Platelet Glycoprotein GPIb-IX Complex
Glycoproteins
Latex
Platelets
Latexes
Microspheres
Platelet Aggregation
Shear deformation
Fibrinogen
Blood Platelets
Agglomeration
Platelet Membrane Glycoproteins
Administrative data processing
von Willebrand Factor
Hemostatics
Collagen
Thrombocytopenia
Nanoparticles
Adenosine Diphosphate
Thrombosis

Keywords

  • Fibrinogen γ-chain dodecapeptide
  • Platelet glycoprotein (GP) Ibα
  • Platelet substitute
  • Shear rate
  • Thrombocytopenia-imitation blood

ASJC Scopus subject areas

  • Biophysics

Cite this

New strategy of platelet substitutes for enhancing platelet aggregation at high shear rates : Cooperative effects of a mixed system of fibrinogen γ-chain dodecapeptide- or glycoprotein Ibα-conjugated latex beads under flow conditions. / Okamura, Yosuke; Handa, Makoto; Suzuki, Hidenori; Ikeda, Yasuo; Takeoka, Shinji.

In: Journal of Artificial Organs, Vol. 9, No. 4, 12.2006, p. 251-258.

Research output: Contribution to journalArticle

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