Department of Microbiology and Immunology, David H. Smith Center for Vaccine Biology and Immunology, University of Rochester, 601 Elmwood Avenue, Rochester, NY 14642, USA.
Br J Haematol. 2010 Mar;148(6):817-33. doi: 10.1111/j.1365-2141.2009.08020.x. Epub 2009 Dec 8.
Activated protein C (APC) is a natural anticoagulant that plays an important role in coagulation homeostasis by inactivating the procoagulation factor Va and VIIIa. In addition to its anticoagulation functions, APC also has cytoprotective effects such as anti-inflammatory, anti-apoptotic, and endothelial barrier protection. Recently, a recombinant form of human APC (rhAPC or drotrecogin alfa activated; known commercially as 'Xigris') was approved by the US Federal Drug Administration for treatment of severe sepsis associated with a high risk of mortality. Sepsis, also known as systemic inflammatory response syndrome (SIRS) resulting from infection, is a serious medical condition in critical care patients. In sepsis, hyperactive and dysregulated inflammatory responses lead to secretion of pro- and anti-inflammatory cytokines, activation and migration of leucocytes, activation of coagulation, inhibition of fibrinolysis, and increased apoptosis. Although initial hypotheses focused on antithrombotic and profibrinolytic functions of APC in sepsis, other agents with more potent anticoagulation functions were not effective in treating severe sepsis. Furthermore, APC therapy is also associated with the risk of severe bleeding in treated patients. Therefore, the cytoprotective effects, rather than the anticoagulant effect of APC are postulated to be responsible for the therapeutic benefit of APC in the treatment of severe sepsis.
活化蛋白 C（APC）是一种天然抗凝剂，通过失活促凝血因子 Va 和 VIIIa 在凝血稳态中发挥重要作用。除了抗凝功能外，APC 还具有细胞保护作用，如抗炎、抗凋亡和内皮屏障保护。最近，一种重组人 APC（rhAPC 或 drotrecogin alfa 激活；商业上称为'Xigris'）被美国联邦药物管理局批准用于治疗伴有高死亡率风险的严重败血症。败血症，也称为感染引起的全身炎症反应综合征（SIRS），是危重病患者中的一种严重医疗状况。在败血症中，过度活跃和失调的炎症反应导致促炎和抗炎细胞因子的分泌、白细胞的激活和迁移、凝血的激活、纤维蛋白溶解的抑制和细胞凋亡的增加。尽管最初的假设集中在 APC 治疗败血症中的抗血栓形成和纤维蛋白溶解作用，但其他具有更强抗凝作用的药物在治疗严重败血症方面并不有效。此外，APC 治疗也与治疗患者严重出血的风险相关。因此，APC 治疗严重败血症的治疗益处被认为与其细胞保护作用，而不是抗凝作用有关。
