Hoffman J N, Faist E
Department of Surgery, Klinikum Grosshadern, Ludwig-Maximilians University, Munich, Germany.
Crit Care Med. 2000 Sep;28(9 Suppl):S74-6. doi: 10.1097/00003246-200009001-00016.
Because coagulatory activation in sepsis is triggered mainly by tissue factor release from endothelial cells and blood monocytes during their activation via proinflammatory cytokines, inhibition of coagulation by exogenous administration of coagulation inhibitors has been proposed. These strategies should allow us to prevent and treat excessive coagulatory activation, thereby potentially preventing sepsis-induced organ dysfunction. Potential therapies include the natural coagulation inhibitors antithrombin, activated protein C, and tissue factor pathway inhibitor, as well as direct thrombin inhibition by recombinant hirudin.
A limited review of the published literature using all sources was undertaken.
Selected clinical and experimental studies with coagulatory inhibitors were analyzed.
The biological properties of coagulatory activation during sepsis (coagulation as a protective mechanism to control the septic focus, e.g., fibrin deposition during peritonitis) are not completely understood. Therefore, one has to be careful when administering coagulatory inhibitors, especially because patients with multiple organ dysfunction syndrome often do not show the widespread fibrin deposition in nutritive blood vessels that have been seen experimentally. How might these patients benefit from thrombin inhibition? Coagulatory activation per se seems unlikely to directly cause deterioration of organ function, although it is involved in generalized endothelial activation with consecutive mediator release and increased leukocyte-endothelial cell interaction. Antagonism of inflammatory mediators and, consecutively, endothelial cell activation might be a better target in adjunctive sepsis therapy, with improvement in septic microcirculatory disturbances. Administration of natural pleiotropic coagulation inhibitors that are documented positive effects on the microcirculation, (such as activated protein C, antithrombin) seems to be promising.
由于脓毒症中的凝血激活主要是由内皮细胞和血液单核细胞在通过促炎细胞因子激活过程中释放组织因子所触发，因此有人提出通过外源性给予凝血抑制剂来抑制凝血。这些策略应能使我们预防和治疗过度的凝血激活，从而有可能预防脓毒症诱导的器官功能障碍。潜在的治疗方法包括天然凝血抑制剂抗凝血酶、活化蛋白C和组织因子途径抑制剂，以及重组水蛭素对凝血酶的直接抑制作用。
对所有来源的已发表文献进行了有限的综述。
分析了选定的使用凝血抑制剂的临床和实验研究。
脓毒症期间凝血激活的生物学特性（凝血作为控制脓毒症病灶的一种保护机制，例如腹膜炎期间的纤维蛋白沉积）尚未完全了解。因此，在使用凝血抑制剂时必须谨慎，特别是因为多器官功能障碍综合征患者通常不会出现实验中所见的营养血管广泛纤维蛋白沉积。这些患者如何能从凝血酶抑制中获益？凝血激活本身似乎不太可能直接导致器官功能恶化，尽管它参与了全身性内皮细胞激活以及随之而来的介质释放和白细胞与内皮细胞相互作用的增加。在辅助性脓毒症治疗中，拮抗炎症介质以及随之而来的内皮细胞激活可能是一个更好的靶点，可改善脓毒症性微循环障碍。给予对微循环有积极作用记录的天然多效性凝血抑制剂（如活化蛋白C、抗凝血酶）似乎很有前景。
