The GPIb thrombin-binding site is essential for thrombin-induced platelet procoagulant activity

Paul S. Frenette, Linnea Weiss

Research output: Contribution to journalArticle

152 Citations (Scopus)

Abstract

The role of the platelet glycoprotein (GP) Ib-V-IX receptor in thrombin activation of platelets has remained controversial although good evidence suggests that blocking this receptor affects platelet responses to this agonist. The mechanism of expression of procoagulant activity in response to platelet agonists is also still obscure. Here, the binding site for thrombin on GPIb is shown to have a key role in the exposure of negatively charged phospholipids on the platelet surface and thrombin generation, in response to thrombin, which also requires protease-activated receptor-1, GPIIb-IIIa, and platelet-platelet contact. Von Willebrand factor binding to GPIb is not essential to initiate development of platelet procoagulant activity. Inhibition of fibrinogen binding to GPIIb-IIIa also failed to block platelet procoagulant activity. Both heparin and low molecular weight heparin block thrombin-induced platelet procoagulant activity, which may account for part of their clinical efficacy. This study demonstrates a new, critical role for platelet GPIb in hemostasis, showing that platelet activation and coagulation are tightly interwoven, which may have implications for alternative therapies for thrombotic diseases. (C) 2000 by The American Society of Hematology.

Original languageEnglish (US)
Pages (from-to)2469-2478
Number of pages10
JournalBlood
Volume96
Issue number7
StatePublished - Oct 1 2000
Externally publishedYes

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Platelets
Thrombin
Blood Platelets
Binding Sites
Platelet Activation
PAR-1 Receptor
Platelet Glycoprotein GPIb-IX Complex
Thrombin Receptors
Platelet Membrane Glycoproteins
Chemical activation
Low Molecular Weight Heparin
von Willebrand Factor
Complementary Therapies
Hemostasis
Fibrinogen
Heparin
Phospholipids
Coagulation

ASJC Scopus subject areas

  • Hematology

Cite this

The GPIb thrombin-binding site is essential for thrombin-induced platelet procoagulant activity. / Frenette, Paul S.; Weiss, Linnea.

In: Blood, Vol. 96, No. 7, 01.10.2000, p. 2469-2478.

Research output: Contribution to journalArticle

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