The GPIb thrombin-binding site is essential for thrombin-induced platelet procoagulant activity
The GPIb thrombin-binding site is essential for thrombin-induced platelet procoagulant activity
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DOI：
10.1182/blood.v96.7.2469.h8002469_2469_2478
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发表时间：
2000-10-01
期刊：
影响因子：
20.3
通讯作者：
Kehrel, BE
中科院分区：
文献类型：
--
作者：
Dörmann, D;Clemetson, KJ;Kehrel, BE
血小板糖蛋白（GP）Ib-V-IX受体在血小板的凝血酶活化中的作用仍然存在争议，尽管有充分的证据表明阻断该受体会影响血小板对该激动剂的反应。在这里，GPIb上凝血酶的结合位点被证明在血小板表面上带负电荷的磷脂的暴露和凝血酶的产生中具有关键作用，以响应凝血酶，这也需要蛋白酶激活的受体-1，GPIIb-IIIa和血小板-血小板接触。血管性血友病因子与GPIb的结合对血小板促凝活性的启动并不重要。抑制纤维蛋白原与GPIIb-IIIa的结合也未能阻断血小板促凝活性。肝素和低分子量肝素都能阻断凝血酶诱导的血小板促凝活性，这可能是其临床疗效的一部分。这项研究证明了血小板GPIb在止血中的一个新的关键作用，表明血小板活化和凝血是紧密交织在一起的，这可能对血栓性疾病的替代疗法产生影响。（血。2000;96：2469-2478）（C）2000由美国血液学学会。
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. (Blood. 2000;96:2469-2478) (C) 2000 by The American Society of Hematology.