血液凝固：止血与凝血酶调节

围手术期出血是一个棘手的问题，尤其是伴随着强效抗凝药物临床应用的日趋增多，这一问题变得更具挑战性。理解和掌握当今的凝血概念对于手术前确定患者固手术期的出血风险并在固手术期给予有效的止血治疗十分重要。具有丝氨酸蛋白酶活性的凝血酶在激活其他丝氧酸蛋白酶原（无活性的酶前体）、辅助因子和细胞表面受体的过程中发挥着关键的作用。机体在遭受创伤后通过对凝血酶生成的严密调控可以获得局部快速止血而无全身不可控血栓形成的效果。手术期间，出血／血液稀释、输血和手术应激可以严重干扰凝血和炎性反应系统。手术后出血常常需要输注同种异体血治疗，这促进了凝血酶的产生与止血作用。但是手术后促凝血物质的活性和炎性反应也同时增加。因此，可能需要采用抗血栓治疗来预防围手术期血栓性并发症。新型止血药和抗血栓形成药物的开发应用使得围手术期止血管理和防治血栓形成方面取得了很大的进步。然而，当前治疗的局限性在于，传统的凝血检查并不能反映整个凝血过程，使得对药物治疗进行优化变得比较困难。理解凝血酶生成的体内调节机制和药物调控可能有助于在不增加促血栓生成风险的条件下控制出血。在这篇综述里，我们采用多种简化凝血模型对止血和凝血酶形成的调节机制进行探讨。

Perioperative bleeding is a major challenge particularly because of increasing clinical use of potent antamrombotic drugs. Understanding current concepts of coagulation is important in determining the preoperative bleeding risk of patients, and in managing hemostatic therapy perioperatively. The serine protease thrombin plays pivotal roles in the activation of additional serine protease zymogens （inactive enzymatic precursors）, cofactors, and cell-surface receptors. Thrombin generation is closely regulated to locally achieve rapid hemostasis after injury without causing uncontrolled systemic thrombosis. During surgery, there are major disturbances in coagulation and inflammatory systems because of hemorrhage/hemodilution, blood transfusion, and surgical stresses. Postoperative bleeding often requires allogeneic blood transfusions, which support thrombin generation and hemostasis. However, procoagulant actixdty and inflammation are increased postoperatively; thus, antithrombotic therapy may be required to prevent perioperative thrombotic complications. There have been significant advances in the management of perioperative hemostasis and thrombosis because of the introduction of novel hemostatic and antithrombotic drugs. However, a limitation of current treatment is that conventional dotting tests do not reflect the entire physiological processes of coagulation making optimal pharmacologic therapy difficult. Understanding the in vivo regulatory mechanisms and pharmacologic modulation of thrombin generation may help control bleeding without potentially increasing prothrombotic risks. In this review, we focus on the regulatory mechanisms of hemostasis and thrombin generation using multiple, simplified models of coagulation.