The impact of the inflammatory response on coagulation
The impact of the inflammatory response on coagulation
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DOI：
10.1016/j.thromres.2004.06.028
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发表时间：
2004-01-01
影响因子：
7.5
通讯作者：
Esmon, CT
中科院分区：
文献类型：
--
作者：
Esmon, CT
炎症对血栓形成反应的影响涉及细胞和体液调节。炎症影响血液凝固的起始、传播和抑制阶段。内毒素和肿瘤坏死因子α（TNF -α）等炎症介质会诱导血细胞上组织因子的表达。在正常情况下，带负电荷的膜表面是有限的，因此，即使产生了一些活化的凝血因子，凝血刺激的传播也是极小的。然而，补体激活，或者胶原蛋白与凝血酶结合暴露，会提供一种强大的刺激，导致带负电荷的磷脂膜表面暴露。天然抗凝机制限制血栓形成反应，但这些途径会被炎症介质抑制。蛋白C途径是主要的靶点之一。血栓调节蛋白和内皮细胞蛋白C受体对于蛋白C的最佳活化都是必需的，但两者都会被炎症介质下调。此外，游离蛋白S水平常常降低，导致所产生的活化蛋白C的抗凝功能受损。另外，抗磷脂抗体严重损害蛋白C途径，在与自身免疫相关的炎症状态下进一步抑制该途径。除了使止血系统倾向于凝血形成外，炎症还会提高纤溶酶原激活物抑制剂的水平，从而降低纤溶活性。炎症的促凝血作用在细胞水平也可见。白细胞介素6等炎症介质可增加血小板数量及其对凝血酶等激动剂的反应性。所有这些事件都倾向于使止血平衡向有利于凝血形成的方向转变。（c）2004爱思唯尔有限公司。保留所有权利。
Inflammation contributions to the thrombotic response involve both cellular and humoral modulation. Inflammation impacts the initiation, propagation and the inhibitory phases of blood coagulation. Inflammatory mediators like endotoxin and tumor necrosis factor alpha (TNF alpha) elicit the expression of tissue factor on blood cells. Under normal circumstance, negatively charged membrane surfaces are limiting so that, even if some activated coagulation factors are generated, propagation of the coagulant stimulus is minimal. Complement activation, however, or exposure of collagen in combination with thrombin, provides a potent stimulus eliciting the exposure of negatively charged phospholipid membrane surfaces. Natural anticoagulant mechanisms limit the thrombotic response, but these pathways are depressed by inflammatory mediators. The protein C pathway is one of the major targets. Thrombomodulin and the endothelial cell protein C receptor are both required for optimal protein C activation, but both are down regulated by inflammatory mediators. Furthermore, free protein S levels often decrease resulting in impaired anticoagulant function of the activated protein C that is generated. In addition, anti-phosphotipid antibodies severely impair the protein C pathway further inhibiting this pathway in inflammatory states associated with auto-immunity. In addition to shifting the hemostatic system in favor of clot formation, inflammation elevates the levels of plasminogen activator inhibitor thereby decreasing fibrinolytic activity. The procoagulant impact of inflammation can also be seen at the cellular level. Inflammatory mediators like interleukin 6 can increase both platelet count and their responsiveness to agonists like thrombin. All of these events tend to shift the hemostatic balance in favor of clot formation. (c) 2004 Elsevier Ltd. All rights reserved.