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

Dörmann, D; Clemetson, KJ; Kehrel, BE (2000). The GPIb thrombin-binding site is essential for thrombin-induced platelet procoagulant activity. Blood, 96(7), pp. 2469-78. Washington, D.C.: American Society of Hematology

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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.

Item Type:

Journal Article (Original Article)

Division/Institute:

04 Faculty of Medicine > Pre-clinic Human Medicine > Theodor Kocher Institute

UniBE Contributor:

Clemetson, Kenneth John

ISSN:

0006-4971

ISBN:

11001899

Publisher:

American Society of Hematology

Language:

English

Submitter:

Factscience Import

Date Deposited:

04 Oct 2013 14:52

Last Modified:

04 May 2014 23:15

PubMed ID:

11001899

Web of Science ID:

000089552500023

URI:

https://boris.unibe.ch/id/eprint/22172 (FactScience: 32192)

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