Caldwell Stephen H, Hoffman Maureane, Lisman Ton, Macik B Gail, Northup Patrick G, Reddy K Rajender, Tripodi Armando, Sanyal Arun J
University of Virginia, Digestive Health Center of Excellence, GI/Hepatology Division, Charlottesville, VA 22908-0705, USA.
Hepatology. 2006 Oct;44(4):1039-46. doi: 10.1002/hep.21303.
Normal coagulation has classically been conceptualized as a Y-shaped pathway, with distinct "intrinsic" and "extrinsic" components initiated by factor XII or factor VIIa/tissue factor, respectively, and converging in a "common" pathway at the level of the FXa/FVa (prothrombinase) complex. Until recently, the lack of an established alternative concept of hemostasis has meant that most physicians view the "cascade" as a model of physiology. This view has been reinforced by the fact that screening coagulation tests (APTT, prothrombin time--INR) are often used as though they are generally predictive of clinical bleeding. The shortcomings of this older model of normal coagulation are nowhere more apparent than in its clinical application to the complex coagulation disorders of acute and chronic liver disease. In this condition, the clotting cascade is heavily influenced by numerous currents and counter-currents resulting in a mixture of pro- and anticoagulant forces that are themselves further subject to change with altered physiological stress such as super-imposed infection or renal failure. This report represents a summary of a recent multidisciplinary symposium held in Charlottesville, VA. We present an overview of the coagulation system in liver disease with emphasis on the limitations of the current clinical paradigm and the need for a critical re-evaluation of the current tenets governing clinical practice. With the realization that there is often limited or conflicting data, we have attempted to represent diverse opinion and experience from the perspectives of both hepatology and hematology beginning with a brief update on the physiology of normal coagulation.
传统上，正常凝血被概念化为一个Y形途径，分别由因子XII或因子VIIa/组织因子启动不同的“内源性”和“外源性”成分，并在FXa/FVa（凝血酶原酶）复合物水平汇聚于“共同”途径。直到最近，由于缺乏已确立的止血替代概念，大多数医生将“瀑布学说”视为一种生理学模型。凝血筛查试验（活化部分凝血活酶时间、凝血酶原时间-国际标准化比值）常被用作似乎能普遍预测临床出血情况，这一事实进一步强化了这种观点。这种旧的正常凝血模型的缺点在其应用于急性和慢性肝病复杂凝血障碍的临床实践中最为明显。在这种情况下，凝血瀑布受到众多正向和反向作用的严重影响，导致促凝和抗凝力量混合，而这些力量本身又会随着诸如叠加感染或肾衰竭等生理应激改变而进一步变化。本报告是弗吉尼亚州夏洛茨维尔最近举行的一次多学科研讨会的总结。我们概述了肝病中的凝血系统，重点强调了当前临床范式的局限性以及对指导临床实践的当前原则进行批判性重新评估的必要性。鉴于认识到数据往往有限或相互矛盾，我们试图从肝病学和血液学的角度展现不同的观点和经验，首先简要更新正常凝血的生理学知识。
