Okajima K, Koga S, Kaji M, Inoue M, Nakagaki T, Funatsu A, Okabe H, Takatsuki K, Aoki N
Department of Laboratory Medicine, Kumamoto University Medical School, Japan.
Thromb Haemost. 1990 Feb 19;63(1):48-53.
Although protein C (PC) and activated protein C (APC) have been postulated to be useful for treating patients with thrombosis, their critical effect remains to be studied in human subjects. To examine whether purified PC or APC are useful for treating patients with thrombosis without showing any adverse effect, we studied effects on coagulation and fibrinolysis in normal human subjects. When highly purified human PC was administered intravenously to healthy subjects, plasma levels of immunoreactive PC decreased with a half-life of 10.9 h. Intravenously administered APC decreased with a half-life of 23 min as measured by prolongation of activated partial thromboplastin time (APTT). However, 1.7 h was obtained for the plasma half-life of APC when it was measured immunologically. These findings suggested that a significant fraction of the administered APC was rapidly inhibited by plasma inhibitor. Upon administration of APC, APTT was prolonged and plasma levels of clotting factor VIII (F-VIII) decreased transiently as measured by clotting assay. However, when determined by a chromogenic assay method in which 120-fold diluted plasma samples were used, plasma levels of F-VIII remained unchanged. Plasma levels of F-V did not decrease after APC administration. These findings suggested that prolongation of APTT and apparent decrease in plasma F-VIII clotting activity might be due to the in vitro-effect of APC present in plasma samples used. Diurnal fluctuation of plasminogen activator inhibitor in normal subject was not affected by administration of APC. Thus, PC or APC seems to function selectively at the site of thrombin-formation without lowering plasma levels of coagulation factors.
尽管蛋白C（PC）和活化蛋白C（APC）被推测可用于治疗血栓形成患者，但其关键作用仍有待在人体中进行研究。为了检验纯化的PC或APC是否可用于治疗血栓形成患者而不产生任何不良反应，我们研究了其对正常人体受试者凝血和纤溶的影响。当将高度纯化的人PC静脉注射给健康受试者时，免疫反应性PC的血浆水平下降，半衰期为10.9小时。通过活化部分凝血活酶时间（APTT）延长来测量，静脉注射的APC半衰期为23分钟。然而，通过免疫学方法测量时，APC的血浆半衰期为1.7小时。这些发现表明，所给予的APC中有很大一部分被血浆抑制剂迅速抑制。给予APC后，APTT延长，通过凝血试验测量，凝血因子VIII（F-VIII）的血浆水平短暂下降。然而，当使用120倍稀释的血浆样本通过发色测定法测定时，F-VIII的血浆水平保持不变。给予APC后，F-V的血浆水平没有下降。这些发现表明，APTT的延长和血浆F-VIII凝血活性的明显下降可能是由于所用血浆样本中存在的APC的体外效应。正常受试者中纤溶酶原激活物抑制剂的昼夜波动不受APC给药的影响。因此，PC或APC似乎在凝血酶形成部位选择性发挥作用，而不会降低凝血因子的血浆水平。
