Satran Robert, Almog Yaniv
Medical Intensive Care Unit, Soroka University Hospital and Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer Sheva, Israel.
Isr Med Assoc J. 2003 Jul;5(7):516-20.
Sepsis is an infection-induced inflammatory syndrome that results in a complex network of adaptive and maladaptive alterations in homeostatic mechanisms. Severe sepsis, defined as sepsis associated with acute organ failure, is a serious disease with a mortality rate of 30-50%. The coagulation system, through complex interactions, has an important role in the final outcome of the sepsis-induced inflammatory cascade. A fine and delicate balance that normally exists between anticoagulant mechanisms and the procoagulant response is altered in sepsis. Activated protein C, an endogenous vitamin K-dependent anticoagulant, plays a major role in the down-regulation of the procoagulant arm. It also possesses anti-inflammatory properties. Endothelial damage during sepsis impairs the endothelium-dependent activation of protein C, thus shifting the balance towards thrombosis. This shift may contribute to the development of sepsis-related multi-organ failure. Evidence suggesting that activation of the coagulation system may contribute to sepsis-related morbidity and mortality has led to extensive research attempting to correct the hemostatic defects seen in septic patients. Indeed, a recent randomized controlled trial demonstrated a reduction in overall mortality in patients with severe sepsis treated with APC. In this review we discuss the pathogenesis of the coagulopathy of sepsis, as well as the new therapeutic approaches aimed at correcting the defects in the coagulation system.
脓毒症是一种由感染引起的炎症综合征，可导致体内稳态机制出现适应性和非适应性改变的复杂网络。严重脓毒症定义为与急性器官功能衰竭相关的脓毒症，是一种严重疾病，死亡率为30%至50%。凝血系统通过复杂的相互作用，在脓毒症诱导的炎症级联反应的最终结果中起重要作用。脓毒症时，抗凝机制与促凝反应之间通常存在的精细平衡被打破。活化蛋白C是一种内源性维生素K依赖的抗凝剂，在下调促凝途径中起主要作用。它还具有抗炎特性。脓毒症期间的内皮损伤会损害蛋白C的内皮依赖性激活，从而使平衡向血栓形成方向偏移。这种偏移可能导致脓毒症相关的多器官功能衰竭。有证据表明凝血系统的激活可能导致脓毒症相关的发病率和死亡率，这促使人们进行广泛研究，试图纠正脓毒症患者出现的止血缺陷。事实上，最近一项随机对照试验表明，用活化蛋白C治疗的严重脓毒症患者的总体死亡率有所降低。在这篇综述中，我们讨论了脓毒症凝血病的发病机制，以及旨在纠正凝血系统缺陷的新治疗方法。
