第十四章凝血和抗凝血平衡紊乱.ppt

五、DIC防治的病理生理学基础 1、防治原发病 2、改善微循环（早期） 3、建立新的凝血纤溶间的动态平衡 抗凝治疗 补充凝血因子 抗纤溶治疗 * In patients with disseminated intravascular coagulation, fibrin is formed as a result of the generation of thrombin mediated by tissue factor. Tissue factor, expressed on the surface of activated mononuclear cells and endothelial cells, binds and activates factor VII. The complex of tissue factor and factor VIIa can activate factor X directly (black arrows) or indirectly (white arrows) by means of activated factor IX and factor VIII. Activated factor X, in combination with factor V, can convert prothrombin (factor II) to thrombin (factor IIa). Simultaneously, all three physiologic means of anticoagulation — antithrombin III, protein C, and tissue factor–pathway inhibitor (TFPI) — are impaired. The resulting intravascular formation of fibrin is not balanced by adequate removal of fibrin because endogenous fibrinolysis is suppressed by high plasma levels of plasminogen-activator inhibitor type 1 (PAI-1). The high levels of PAI-1 inhibit plasminogen-activator activity and consequently reduce the rate of formation of plasmin. The combination of increased formation of fibrin and inadequate removal of fibrin results in disseminated intravascular thrombosis. FDPs denotes fibrin-degradation products. * DIC在临床可表现为急性全身性，也可为亚急性、慢性，主要发生在脏器局部。对机体造成严重危害的是急性全身性DIC。DIC发病率约0.2‰~0.5‰，因其早期不易诊断，且治疗复杂，急性全身性DIC死亡率高达50%~60%，是一种严重威胁患者生命的临床综合征。 DIC的发病机制 RBC破坏，释放大量ADP，促进血小板粘附，聚集 WBC破坏释放TF样物质，WBC受刺激表达TF PLT激活、粘附、聚集，促进凝血 血细胞的大量破坏，血小板被激活 DIC的发病机制 急性坏死性胰腺炎，胰蛋白酶入血激活凝血酶原 蛇毒激活FⅤ，FⅩ等，促进DIC发生 肿瘤细胞分泌促凝物质 羊水中含有组织因子样物质 内毒素刺激VEC表达TF，损伤VEC 促凝物质释放入血 严重感染引起DIC的发病机制 感染时产生的细胞因子作用于内皮细胞可使TF表达增加；而同时又可使内皮细胞上的血栓调节蛋白、硫酸乙酰肝素的表达明显减少 内毒素可损伤血管内皮细胞，同时释放血小板激活剂，促进血小板的活化、聚集。 白细胞激活可释放炎症介质，损伤血管内皮细胞 细胞因子可使血管内皮细胞产生tPA减少，而PAI-1产生增多。 二、影响DIC发生发展的因素 吞噬、清除血液中的凝血酶，纤维蛋白等促凝物 清除纤溶酶，FDP，内毒素等 坏死组织，细菌等“封闭”其功能 全身性Shwartzman反应 单核巨噬细胞系统功能受损 影响DIC发生发展的因素 蛋白C、AT-Ⅲ、纤溶酶原等合成减少 凝血因子的灭活障碍 肝细胞坏死，释放TF 肝功能严重障碍 影响D