Heparin inhibition of von Willebrand factor-dependent platelet function in vitro and in vivo.
Heparin inhibition of von Willebrand factor-dependent platelet function in vitro and in vivo.
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肝素在体外和体内抑制血管性血友病因子依赖性血小板功能。
DOI：
10.1172/jci115198
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发表时间：
1991
期刊：
影响因子：
--
通讯作者：
Marques,D
中科院分区：
文献类型：
--
作者：
Sobel,M;McNeill,PM;Carlson,PL;Kermode,JC;Adelman,B;Conroy,R;Marques,D
心内直视手术前静脉注射肝素可降低58%的血管紧张素转换酶辅因子活性（P <0.01，t检验），这种血管性血友病因子依赖性血小板功能的损害与血浆肝素水平密切相关（r2 = 0.9），但与血浆血管性血友病因子（vWF）水平无关。我们假设肝素可能通过直接结合溶液中的vWF并干扰vWF-GpIb结合来抑制vWF依赖性血小板止血功能。使用在体外技术瑞斯托霉素诱导的血小板凝集，荧光流式细胞术测量vWF-血小板结合，和传统的放射性配体结合试验，我们观察到肝素抑制vWF依赖性血小板功能和vWF-血小板结合在一个平行的和剂量依赖性的方式。肝素还抑制牛vWF诱导的血小板凝集，并抑制人去唾液酸vWF与无瑞斯托菌素系统中血小板的结合。肝素的抑制效力不依赖于其对抗凝血酶III的亲和力，但依赖于分子量：低分子量的均质制剂抑制性较低。肝素对vWF功能的损害可以解释为什么根据监测肝素常规抗凝作用的技术，肝素治疗的一些出血性并发症是不可预测的。
The intravenous administration of heparin to patients before open heart surgery reduced ristocetin cofactor activity by 58% (P less than 0.01, t test), and this impairment of von Willebrand factor-dependent platelet function was closely related to plasma heparin levels (r2 = 0.9), but not to plasma von Willebrand factor (vWF) levels. We hypothesized that heparin may inhibit vWF-dependent platelet hemostatic functions by directly binding vWF in solution and interfering with vWF-GpIb binding. Using the in vitro techniques of ristocetin-induced platelet agglutination, fluorescent flow cytometric measurement of vWF-platelet binding, and conventional radioligand binding assays we observed that heparin inhibited both vWF-dependent platelet function and vWF-platelet binding in a parallel and dose-dependent manner. Heparin also inhibited platelet agglutination induced by bovine vWF and inhibited the binding of human asialo-vWF to platelets in ristocetin-free systems. The inhibitory potency of heparin was not dependent upon its affinity for antithrombin III, but was molecular weight dependent: homogeneous preparations of lower molecular weight were less inhibitory. Heparin impairment of vWF function may explain why some hemorrhagic complications of heparin therapy are not predictable based on techniques for monitoring the conventional anticoagulant effects of heparin.