Coagulation in Patients with Severe Sepsis
Coagulation in Patients with Severe Sepsis
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DOI：
10.1055/s-0034-1398376
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发表时间：
2015-02-01
影响因子：
5.7
通讯作者：
van der Poll, Tom
中科院分区：
文献类型：
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作者：
Levi, Marcel;van der Poll, Tom
在大多数严重脓毒症患者中，存在全身凝血激活。越来越多的证据表明，凝血和炎症之间广泛的相互作用可能在败血症的发病机制中起重要作用。炎症不仅会激活凝血，凝血也会显著影响炎症活动。有助于炎症诱导的凝血激活的分子途径已经被精确地确定。促炎细胞因子和其他介质能够激活凝血系统并下调重要的生理抗凝途径。凝血系统的激活和随后凝血酶的产生依赖于组织因子在活化的单核细胞和内皮细胞上的表达，TFPI无法充分抵消。同时，内皮结合的抗凝机制，特别是蛋白C系统，被促炎细胞因子关闭。此外，由于纤维蛋白溶解系统的失活，其主要抑制剂纤溶酶原激活物抑制剂1型（PAI-1）的上调导致纤维蛋白去除受到严重抑制。纤维蛋白形成增加和去除受损导致（微）血管血栓形成，这可能导致组织缺血和随后的器官损伤。脓毒症中凝血治疗的基石是对潜在疾病的特异性和有力治疗。旨在抑制凝血激活的策略在理论上可能是合理的，并且在实验和初步临床研究中发现是有益的。肝素可能是一种有效的抗凝方法，替代策略包括恢复生理抗凝途径。
In the majority of patients with severe sepsis, systemic activation of coagulation is present. Increasing evidence points to an extensive cross-talk between coagulation and inflammation that may play an important role in the pathogenesis of sepsis. Inflammation not only leads to activation of coagulation, but coagulation also considerably affects inflammatory activity. Molecular pathways that contribute to inflammation-induced activation of coagulation have been precisely identified. Proinflammatory cytokines and other mediators are capable of activating the coagulation system and downregulating important physiological anticoagulant pathways. Activation of the coagulation system and ensuing thrombin generation is dependent on expression of tissue factor on activated mononuclear cells and endothelial cells, and is insufficiently counteracted by TFPI. Simultaneously, endothelial-bound anticoagulant mechanism, in particular the protein C system, is shutoff by proinflammatory cytokines. In addition, fibrin removal is severely inhibited, because of inactivation of the fibrinolytic system, caused by an upregulation of its main inhibitor, plasminogen activator inhibitor type 1 (PAI-1). Increased fibrin formation and impaired removal lead to (micro) vascular thrombosis, which may result in tissue ischemia and subsequent organ damage. The cornerstone of the management of coagulation in sepsis is the specific and vigorous treatment of the underlying disorder. Strategies aimed at the inhibition of coagulation activation may theoretically be justified and have been found beneficial in experimental and initial clinical studies. Heparin may be an effective anticoagulant approach and alternative strategies comprise restoration of physiological anticoagulant pathways.