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

The role of the platelet glycoprotein (GP) Ib-V-IX receptor in thrombin act ivation of platelets has remained controversial although good evidence sugg ests that blocking this receptor affects platelet responses to this agonist , The mechanism of expression of procoagulant activity in response to plate let 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 phos pholipids on the platelet surface and thrombin generation, in response to t hrombin, which also requires protease-activated receptor-1, GPIIb-IIIa, and platelet-platelet contact. Von Willebrand factor binding to GPIb is not es sential to initiate development of platelet procoagulant activity. Inhibiti on of fibrinogen binding to GPIIb-IIIa also failed to block platelet procoa gulant activity. Both heparin and low molecular weight heparin block thromb in-induced platelet procoagulant activity, which may account for part of th eir clinical efficacy. This study demonstrates a new, critical role for pla telet GPIb in hemostasis, showing that platelet activation and coagulation are tightly interwoven, which may have implications for alternative therapi es for thrombotic diseases. (Blood. 2000;96:2469-2478) (C) 2000 by The Amer ican Society of Hematology.