VONWILLEBRAND-FACTOR INTERACTION WITH THE GLYCOPROTEIN-IIB GLYCOPROTEIN-IIIA COMPLEX - ITS ROLE IN PLATELET-FUNCTION AS DEMONSTRATED IN PATIENTS WITH CONGENITAL AFIBRINOGENEMIA
VONWILLEBRAND-FACTOR INTERACTION WITH THE GLYCOPROTEIN-IIB GLYCOPROTEIN-IIIA COMPLEX - ITS ROLE IN PLATELET-FUNCTION AS DEMONSTRATED IN PATIENTS WITH CONGENITAL AFIBRINOGENEMIA
复制标题
DOI：
10.1172/jci112430
复制
发表时间：
1986-04-01
影响因子：
15.9
通讯作者：
RUGGERI, ZM
中科院分区：
文献类型：
--
作者：
DEMARCO, L;GIROLAMI, A;RUGGERI, ZM
我们研究了三名无纤维蛋白原血症患者，他们只有微量的血浆和血小板纤维蛋白原，在这里我们证明了他们富含血小板的血浆中观察到的残余聚集依赖于von Willebrand因子(VWF)与血小板膜糖蛋白(GP)IIb/IIIa复合体的结合。当使用ADP而不是凝血酶、胶原或ADP+肾上腺素联合刺激时，聚集的异常更为明显。然而，在所有刺激下，已知可阻断vWF的单抗(LJP5)可完全抑制血小板反应，但不能阻断纤维蛋白原与GPIIb/IIIa的结合。在无纤维蛋白原血浆中加入纯化的vWF可显著增加聚集的速度和程度，尤其是在用ADP刺激血小板时。这一反应也被LJP5完全阻断。然而，即使在LJP5存在的情况下，添加纤维蛋白原也能恢复正常的聚集，这一发现与抗体LJP5对纤维蛋白原与GPIIb/IIIa结合介导的血小板聚集没有影响这一发现一致。两名患者知情同意接受1-去氨基-8-D-精氨酸加压素(DDAVP)的输注，这是一种已知的加压素类似物，可将血浆中的vWF水平提高两到四倍。1例出血时间由注药前>24分钟缩短至12分钟，1例由注药前>24分钟缩短至12分钟，1例由注药后45分钟缩短至50 S，另1例由16分钟缩短至9分钟，出血时间由30 S缩短至30分钟。同时，输注DDAVP后，ADP诱导的血小板聚集率和聚集程度均有所改善。静脉注射DDAVP后，血浆vWF浓度升高，但纤维蛋白原浓度维持在微量水平。我们的结论是，vWF与GPIIb/IIIa的相互作用介导了血小板-血小板的相互作用，并可能在早期止血中发挥作用。
We have studied three afibrinogenemic patients, who had only trace amounts of plasma and platelet fibrinogen as measured by radioimmunoassay, and demonstrate here that the residual aggregation observed in their platelet-rich plasma is dependent upon von Willebrand factor (vWF) binding to the platelet membrane glycoprotein (GP)IIb/IIIa complex. The abnormality of aggregation was more pronounced when ADP, rather than thrombin, collagen, or the combination of ADP plus adrenaline was used to stimulate platelets. With all stimuli, nevertheless, the platelet response was completely inhibited by a monoclonal antibody (LJP5) that is known to block vWF, but not fibrinogen binding to GPIIb/IIIa. Addition of purified vWF to the afibrinogenemic plasma resulted in marked increase in the rate and extent of aggregation, particularly when platelets were stimulated with ADP. This response was also completely blocked by LJP5. Addition of fibrinogen, however, restored normal aggregation even in the presence of LJP5, a finding consistent with the knowledge that antibody LJP5 has no effect on platelet aggregation mediated by fibrinogen binding to GPIIb/IIIa. Two patients gave their informed consent to receiving infusion of 1-desamino-8-D-arginine vasopressin (DDAVP), a vasopressin analogue known to raise the vWF levels in plasma by two- to fourfold. The bleeding time, measured before and 45 min after infusion, shortened from greater than 24 min to 12 min and 50 s in one patient and from 16 min to 9 min and 30 s in the other. Concurrently, the rate and extent of ADP-induced platelet aggregation improved after DDAVP infusion. The pattern, however, reversed to baseline levels within 4 h. The concentration of plasma vWF increased after DDAVP infusion, but that of fibrinogen remained at trace levels. We conclude that vWF interaction with GPIIb/IIIa mediates platelet-platelet interaction and may play a role in primary hemostasis.