Béguin S, Keularts I, Al Dieri R, Bellucci S, Caen J, Hemker H C
Synapse BV, CARIM, University Maastricht, Maastricht, The Netherlands.
J Thromb Haemost. 2004 Jan;2(1):170-6. doi: 10.1111/j.1538-7836.2004.00558.x.
Defective prothrombin consumption has been reported in the proband case of Bernard-Soulier syndrome (BSS). There is no consensus, however, on whether the formation of platelet procoagulant activity (PPA) is impaired in BSS and, if so, whether this is due to the lack of GPIb-V-IX-dependent binding of thrombin or of von Willebrand factor (VWF). We show thrombin generation (TG) in platelet-rich plasma of BSS (BSS-PRP) to be defective provided that fibrin remains present in the reaction mixture and that the giant platelets are not damaged by frequent subsampling. In BSS-PRP addition of (thrombin-free) fibrin did not increase TG as in normal PRP, supporting our previous hypothesis that the interaction of fibrin, VWF and GPIb triggers PPA development. Fibrin formed during the lag phase of TG by a snake venom enzyme which only removed fibrinopeptide A induced an immediate burst of TG, that was inhibited by a monoclonal antibody against GPIb (6D1) that abolishes ristocetin-induced binding of VWF to platelets. Inversely, inhibition of polymerization decreased TG and the residual activity was insensitive to 6D1. We conclude that polymerizing fibrin interacts with VWF so as to activate GPIb.
在伯纳德-苏利耶综合征（BSS）的先证者病例中，已报道凝血酶原消耗存在缺陷。然而，对于BSS中血小板促凝活性（PPA）的形成是否受损，以及如果受损，这是否是由于缺乏凝血酶或血管性血友病因子（VWF）的GPIb-V-IX依赖性结合，目前尚无共识。我们发现，只要反应混合物中仍存在纤维蛋白且巨血小板不因频繁取样而受损，BSS的富血小板血浆（BSS-PRP）中的凝血酶生成（TG）就存在缺陷。在BSS-PRP中添加（无凝血酶的）纤维蛋白并不会像在正常PRP中那样增加TG，这支持了我们之前的假设，即纤维蛋白、VWF和GPIb之间的相互作用触发了PPA的发展。在TG的延迟期由仅去除纤维蛋白肽A的蛇毒酶形成的纤维蛋白诱导了TG的立即爆发，这被一种针对GPIb的单克隆抗体（6D1）所抑制，该抗体消除了瑞斯托菌素诱导的VWF与血小板的结合。相反，抑制聚合作用会降低TG，且残余活性对6D1不敏感。我们得出结论，聚合的纤维蛋白与VWF相互作用以激活GPIb。
