Different effects of various anti-GPIIB-IIIa agents on shear-induced platelet activation and expression of procoagulant activity

S. Goto, N. Tamura, M. Li, M. Handa, Y. Ikeda, S. Handa, Z. M. Ruggri

Research output: Contribution to journalArticle

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Abstract

Inhibitors of the platelet glycoprotein (GP)IIb-IIIa receptor (integrili α IIbβ 3) reduce acute thrombotic events in patients with coronary artery disease. To characterize the mechanism of action of these drugs, we evaluated the effects of different GPIIb-IIIa antagonists on shear-induced platelet aggregation, activation, and the expression of procoagulant activity. Samples of platelet-rich plasma from 16 volunteers were exposed to the shear rate of 10 800 s -1 for 6 min in an optically modified cone-plate viscometer. Abciximab, tirofiban and epti-fibatide inhibited aggregation to a similar extent (mean ± SD: 74.1 ±8.5%, 69.5 ±13.6%, 65.6 ±17.0%, respectively), but only abciximab inhibited significantly microparticle release associated with shear-induced platelet activation (64.4 ± 13.6%, P = 2.2x 10 -7; tirofiban =20.0 ±23.4%; eptifibatide =23.9 ± 17.4%). P-selectin platelet surface translocation was also strongly inhibited by abciximab, weakly by eptifibatide, but not by tirofiban. The addition of anti- α vβ 3 to tirofiban enhanced the inhibiting effects on shear-induced P-selectin translocation and microparticle release. Shearing of platelet-rich plasma shortened the re-calcification clotting time after addition of kaolin from 106.9 ± 14.3 to 94.2 ± 10.7 s (mean ± SD; P = 0.0013). This effect, which is mediated by the appearance of procoagulant phospholipids on the surface of sheared platelets and microparticles, was prevented by abciximab and by the combination of tirofiban and anti-α vβ 3, but not by tirofiban alone or eptifibatide. The ability to inhibit shear-induced platelet activation, as evidenced by microparticle release and P-selectin surface translocation as well as the expression of procoagulant activity, differentiates the effects of anti-GPIIb-IIIa agents, which may explain the distinct antithrom-botic efficacy of the agents.

Original languageEnglish
Pages (from-to)2022-2030
Number of pages9
JournalJournal of Thrombosis and Haemostasis
Volume1
Issue number9
DOIs
Publication statusPublished - 2003 Sep

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tirofiban
Platelet Activation
P-Selectin
Platelet-Rich Plasma
Blood Platelets
Integrin beta3
Kaolin
Platelet Glycoprotein GPIIb-IIIa Complex
Platelet Aggregation
Coronary Artery Disease
Volunteers
Phospholipids

Keywords

  • Glycoproteins
  • Platelets
  • Thrombosis
  • Von Willeb-rand factor

ASJC Scopus subject areas

  • Hematology
  • Medicine(all)

Cite this

Different effects of various anti-GPIIB-IIIa agents on shear-induced platelet activation and expression of procoagulant activity. / Goto, S.; Tamura, N.; Li, M.; Handa, M.; Ikeda, Y.; Handa, S.; Ruggri, Z. M.

In: Journal of Thrombosis and Haemostasis, Vol. 1, No. 9, 09.2003, p. 2022-2030.

Research output: Contribution to journalArticle

Goto, S. ; Tamura, N. ; Li, M. ; Handa, M. ; Ikeda, Y. ; Handa, S. ; Ruggri, Z. M. / Different effects of various anti-GPIIB-IIIa agents on shear-induced platelet activation and expression of procoagulant activity. In: Journal of Thrombosis and Haemostasis. 2003 ; Vol. 1, No. 9. pp. 2022-2030.
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AU - Goto, S.

AU - Tamura, N.

AU - Li, M.

AU - Handa, M.

AU - Ikeda, Y.

AU - Handa, S.

AU - Ruggri, Z. M.

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N2 - Inhibitors of the platelet glycoprotein (GP)IIb-IIIa receptor (integrili α IIbβ 3) reduce acute thrombotic events in patients with coronary artery disease. To characterize the mechanism of action of these drugs, we evaluated the effects of different GPIIb-IIIa antagonists on shear-induced platelet aggregation, activation, and the expression of procoagulant activity. Samples of platelet-rich plasma from 16 volunteers were exposed to the shear rate of 10 800 s -1 for 6 min in an optically modified cone-plate viscometer. Abciximab, tirofiban and epti-fibatide inhibited aggregation to a similar extent (mean ± SD: 74.1 ±8.5%, 69.5 ±13.6%, 65.6 ±17.0%, respectively), but only abciximab inhibited significantly microparticle release associated with shear-induced platelet activation (64.4 ± 13.6%, P = 2.2x 10 -7; tirofiban =20.0 ±23.4%; eptifibatide =23.9 ± 17.4%). P-selectin platelet surface translocation was also strongly inhibited by abciximab, weakly by eptifibatide, but not by tirofiban. The addition of anti- α vβ 3 to tirofiban enhanced the inhibiting effects on shear-induced P-selectin translocation and microparticle release. Shearing of platelet-rich plasma shortened the re-calcification clotting time after addition of kaolin from 106.9 ± 14.3 to 94.2 ± 10.7 s (mean ± SD; P = 0.0013). This effect, which is mediated by the appearance of procoagulant phospholipids on the surface of sheared platelets and microparticles, was prevented by abciximab and by the combination of tirofiban and anti-α vβ 3, but not by tirofiban alone or eptifibatide. The ability to inhibit shear-induced platelet activation, as evidenced by microparticle release and P-selectin surface translocation as well as the expression of procoagulant activity, differentiates the effects of anti-GPIIb-IIIa agents, which may explain the distinct antithrom-botic efficacy of the agents.

AB - Inhibitors of the platelet glycoprotein (GP)IIb-IIIa receptor (integrili α IIbβ 3) reduce acute thrombotic events in patients with coronary artery disease. To characterize the mechanism of action of these drugs, we evaluated the effects of different GPIIb-IIIa antagonists on shear-induced platelet aggregation, activation, and the expression of procoagulant activity. Samples of platelet-rich plasma from 16 volunteers were exposed to the shear rate of 10 800 s -1 for 6 min in an optically modified cone-plate viscometer. Abciximab, tirofiban and epti-fibatide inhibited aggregation to a similar extent (mean ± SD: 74.1 ±8.5%, 69.5 ±13.6%, 65.6 ±17.0%, respectively), but only abciximab inhibited significantly microparticle release associated with shear-induced platelet activation (64.4 ± 13.6%, P = 2.2x 10 -7; tirofiban =20.0 ±23.4%; eptifibatide =23.9 ± 17.4%). P-selectin platelet surface translocation was also strongly inhibited by abciximab, weakly by eptifibatide, but not by tirofiban. The addition of anti- α vβ 3 to tirofiban enhanced the inhibiting effects on shear-induced P-selectin translocation and microparticle release. Shearing of platelet-rich plasma shortened the re-calcification clotting time after addition of kaolin from 106.9 ± 14.3 to 94.2 ± 10.7 s (mean ± SD; P = 0.0013). This effect, which is mediated by the appearance of procoagulant phospholipids on the surface of sheared platelets and microparticles, was prevented by abciximab and by the combination of tirofiban and anti-α vβ 3, but not by tirofiban alone or eptifibatide. The ability to inhibit shear-induced platelet activation, as evidenced by microparticle release and P-selectin surface translocation as well as the expression of procoagulant activity, differentiates the effects of anti-GPIIb-IIIa agents, which may explain the distinct antithrom-botic efficacy of the agents.

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