Scherer R U
Zentrale Abteilung für Anästhesiologie und Intensivmedizin, Evangelisches und Johanniter Klinikum, Duisburg/Dinslaken/Oberhausen gGmbH, Duisberg.
Zentralbl Chir. 2003 Jun;128(6):473-80. doi: 10.1055/s-2003-40620.
Recent studies in humans have shown that tissue factor on the surface of endothelial cells, monocytes, or subendothelial structures sparks plasmatic coagulation. In vivo, there is no functional separation of an "endogenous" and "exogenous" pathway of the coagulation cascade. However, global laboratory tests run along such pathways due to preincubation with specific activators and, hence, allow localization of inherited coagulation defects. Coagulation inhibitors such as antithrombin or activated protein C are accelerated in their activity by cell surface glycoproteins and almost completely inactivate procoagulant activity in the microcirculation. Antithrombin binds to endothelial glycosaminoglycans and then significantly increases anticoagulant activity. Protein C is activated by the thrombin-thrombomodulin-complex and inactivates factors V a and VIII a, respectively. Additionally, activated protein C has a profibrinolytic effect. Both systems physiologically counteract the procoagulant transformation of endothelial and monocyte cell surfaces which occurs in critically ill patients due to induction of tissue factor, suppression of thrombomodulin, and removal of glycosaminoglycans from the cell surface. The distinction of static and dynamic coagulation disorders is useful since static disorders seldom require therapeutic interventions although global laboratory tests may continuously deteriorate. Dynamical disorders are symptoms of an underlying disease, and consumption coagulopathy with disseminated fibrin deposition and oozing occurs when coagulation turnover cannot be stopped. Antithrombin substitution is a well documented therapeutic option along with fresh frozen plasma and erythrocyte concentrate transfusion for blood substitution. Recent case reports in patients with irreversible bleeding complications favour the application of a recombinant factor VII concentrate. A rising perspective to decrease the use of heterologous blood and blood products may be intraoperative plasma retransfusion. The quality of such plasma undergoing consecutive filtration steps has to be clinically studied. The application of a synthetic platelet substitute, the "plateletsome", containing platelet glycoproteins led to significantly improved haemostasis without generating systemic procoagulant activity. In a far future, procoagulant cell surface transformation may be influenced by topic application of inhaled thrombomodulin loaded liposomes or by sense or antisense oligonucleotides inducing thrombomodulin expression or suppressing tissue factor expression, respectively.
近期针对人类的研究表明，内皮细胞、单核细胞表面或内皮下结构上的组织因子可引发血浆凝固。在体内，凝血级联反应的“内源性”和“外源性”途径并无功能上的区分。然而，由于与特定激活剂进行预孵育，全球实验室检测是沿着这些途径进行的，因此能够定位遗传性凝血缺陷。抗凝血酶或活化蛋白C等凝血抑制剂的活性会因细胞表面糖蛋白而加速，并且几乎能完全灭活微循环中的促凝血活性。抗凝血酶与内皮糖胺聚糖结合，进而显著增强抗凝活性。蛋白C由凝血酶 - 血栓调节蛋白复合物激活，分别使因子Va和VIIIa失活。此外，活化蛋白C具有促纤溶作用。这两个系统在生理上可对抗内皮细胞和单核细胞表面的促凝血转变，这种转变在危重症患者中由于组织因子的诱导、血栓调节蛋白的抑制以及细胞表面糖胺聚糖的去除而发生。区分静态和动态凝血障碍是有用的，因为静态障碍很少需要治疗干预，尽管全球实验室检测结果可能持续恶化。动态障碍是潜在疾病的症状，当凝血周转无法停止时，会发生伴有弥散性纤维蛋白沉积和渗血的消耗性凝血病。抗凝血酶替代疗法是一种有充分文献记载的治疗选择，同时新鲜冷冻血浆和红细胞浓缩液输血也是常用的血液替代方法。近期关于不可逆出血并发症患者的病例报告支持应用重组因子VII浓缩物。减少异体血液和血液制品使用的一个有前景的方法可能是术中血浆回输。必须对经过连续过滤步骤的此类血浆质量进行临床研究。应用含有血小板糖蛋白的合成血小板替代物“血小板体”可显著改善止血效果，且不会产生全身性促凝血活性。在遥远的未来，促凝血细胞表面转变可能会受到吸入负载血栓调节蛋白的脂质体的局部应用影响，或者分别受到诱导血栓调节蛋白表达或抑制组织因子表达的正义或反义寡核苷酸的影响。
