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

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

  • Dörmann, Dagmar From the Klinik und Poliklinik für Anästhesiologie und operative Intensivmedizin, Experimental and Clinical Haemostasis, University of Münster, Germany; Theodor Kocher Institute, University of Berne, Switzerland.
  • Clemetson, Kenneth J. From the Klinik und Poliklinik für Anästhesiologie und operative Intensivmedizin, Experimental and Clinical Haemostasis, University of Münster, Germany; Theodor Kocher Institute, University of Berne, Switzerland.
  • Kehrel, Beate E. From the Klinik und Poliklinik für Anästhesiologie und operative Intensivmedizin, Experimental and Clinical Haemostasis, University of Münster, Germany; Theodor Kocher Institute, University of Berne, Switzerland.
Published in:
  • Blood. - American Society of Hematology. - 2000, vol. 96, no. 7, p. 2469-2478
Immunology
Cell Biology
Biochemistry
Hematology
English 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.
Language
  • English
Open access status
closed
Identifiers
Persistent URL
https://folia.unifr.ch/global/documents/285990
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