Dahlbäck Björn
Department of Laboratory Medicine, Division of Clinical Chemistry, Lund University, The Wallenberg Laboratory, University Hospital, Malmö, Malmö, Sweden.
Int J Hematol. 2004 Feb;79(2):109-16. doi: 10.1532/ijh97.03149.
A natural anticoagulant pathway denoted the protein C system provides specific and efficient control of blood coagulation. Protein C is the key component of the system and circulates in the blood as a zymogen to an anticoagulant serine protease. Activation of protein C is achieved on the surface of endothelial cells by thrombin bound to the membrane protein thrombomodulin. The endothelial protein C receptor stimulates the activation of protein C on the endothelium. Activated protein C (APC) modulates blood coagulation by cleaving a limited number of peptide bonds in factor VIIIa (FVIIIa) and factor Va (FVa), cofactors in the activation of factor X and prothrombin, respectively. Vitamin K-dependent protein S stimulates the APC-mediated regulation of coagulation. Not only is protein S involved in the degradation of FVIIIa, but so is FV, which in recent years has been found to be a Janus-faced protein with both procoagulant and anticoagulant potentials. A number of genetic defects affecting the anticoagulant function of the protein C system, eg, APC resistance (Arg506Gln or FV Leiden) and deficiencies of protein C and protein S constitute major risk factors of venous thrombosis. The protein C system also has anti-inflammatory and antiapoptotic potentials, the molecular mechanisms of which are beginning to be unraveled. APC has emerged in recent years as a useful therapeutic compound in the treatment of severe septic shock. The beneficial effect of APC is believed be due to both its anticoagulant and its anti-inflammatory properties.
一种名为蛋白C系统的天然抗凝途径可对血液凝固进行特异性且有效的控制。蛋白C是该系统的关键组成部分，以酶原形式在血液中循环，可转化为抗凝丝氨酸蛋白酶。蛋白C在内皮细胞表面通过与膜蛋白血栓调节蛋白结合的凝血酶实现激活。内皮细胞蛋白C受体可刺激内皮细胞上蛋白C的激活。活化蛋白C（APC）通过切割因子VIIIa（FVIIIa）和因子Va（FVa）中有限数量的肽键来调节血液凝固，FVIIIa和FVa分别是因子X和凝血酶原激活过程中的辅因子。维生素K依赖蛋白S可刺激APC介导的凝血调节。不仅蛋白S参与FVIIIa的降解，FV也参与其中，近年来发现FV是一种具有促凝和抗凝双重潜力的双面蛋白。一些影响蛋白C系统抗凝功能的遗传缺陷，如APC抵抗（Arg506Gln或FV莱顿突变）以及蛋白C和蛋白S缺乏，是静脉血栓形成的主要危险因素。蛋白C系统还具有抗炎和抗凋亡潜力，其分子机制正逐渐被揭示。近年来，APC已成为治疗严重脓毒症休克的一种有效治疗化合物。APC的有益作用被认为是由于其抗凝和抗炎特性。
