Procoagulant activity in hemostasis and thrombosis: Virchow's triad revisited.
Procoagulant activity in hemostasis and thrombosis: Virchow's triad revisited.
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DOI：
10.1213/ane.0b013e31823a088c
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发表时间：
2012-02
影响因子：
5.7
通讯作者：
Machlus KR
中科院分区：
文献类型：
--
作者：
Wolberg AS;Aleman MM;Leiderman K;Machlus KR
Virchow氏三联征传统上被用来解释导致血栓形成的病理生理机制，声称血液成分、血管壁成分和血流异常在动脉和静脉血栓形成中的协同作用。考虑到血友病患者中观察到的组织特异性出血，在研究止血疾病的作用机制时考虑Virchow三联征的原理可能具有指导意义。血液成分（循环血细胞和血浆蛋白的功能）是三联体中研究最充分的组成部分。例如，血浆促凝血蛋白如凝血酶原和纤维蛋白原的水平升高是血栓形成的既定风险因素，而血浆因子VIII和IX的缺乏导致出血（分别为血友病A和B）。血管壁（细胞）组分提供粘附分子，其将循环白细胞和血小板募集到血管损伤部位，组织因子，其提供血管破裂的促凝血信号，以及凝血复合物在其上组装的表面。血流通常由两个关键变量表征：剪切速率和剪切应力。剪切速率影响凝血的几个方面，包括血小板和血浆蛋白进出损伤部位的转运速率、血小板活化以及纤维蛋白单体形成和聚合的动力学。剪切应力调节血小板的粘附率和粘附分子的表达以及血管内皮细胞上的促凝血活性。魏尔啸三联征的任何一个组成部分中没有一个异常可以完全预测凝血病，这表明凝血病是复杂的、多因素的和相互作用的。在这篇综述中，我们着重于血液成分，血管细胞和血流的止血和血栓形成的贡献，并建议魏尔啸的三个组成部分之间的串扰是必要的止血，并确定血栓形成或出血的倾向。研究模型，允许这些组件之间的相互作用是必要的，以了解操作性病理生理学，并有效地治疗和预防血栓形成和出血性疾病。
Virchow’s triad is traditionally invoked to explain pathophysiologic mechanisms leading to thrombosis, alleging concerted roles for abnormalities in blood composition, vessel wall components, and blood flow in the development of arterial and venous thrombosis. Given the tissue-specific bleeding observed in hemophilia patients, it may be instructive to consider the principles of Virchow’s triad when investigating mechanisms operant in hemostatic disorders as well. Blood composition (the function of circulating blood cells and plasma proteins) is the most well-studied component of the triad. For example, increased levels of plasma procoagulant proteins such as prothrombin and fibrinogen are established risk factors for thrombosis, whereas deficiencies in plasma factors VIII and IX result in bleeding (hemophilia A and B, respectively). Vessel wall (cellular) components contribute adhesion molecules that recruit circulating leukocytes and platelets to sites of vascular damage, tissue factor, which provides a procoagulant signal of vascular breach, and a surface upon which coagulation complexes are assembled. Blood flow is often characterized by two key variables: shear rate and shear stress. Shear rate affects several aspects of coagulation, including transport rates of platelets and plasma proteins to and from the injury site, platelet activation, and the kinetics of fibrin monomer formation and polymerization. Shear stress modulates adhesion rates of platelets and expression of adhesion molecules and procoagulant activity on endothelial cells lining the blood vessels. That no one abnormality in any component of Virchow’s triad fully predicts coagulopathy a priori suggests coagulopathies are complex, multifactorial and interactive. In this review, we focus on contributions of blood composition, vascular cells, and blood flow to hemostasis and thrombosis, and suggests cross-talk among the three components of Virchow’s triad is necessary for hemostasis and determines propensity for thrombosis or bleeding. Investigative models that permit interplay among these components are necessary to understand the operant pathophysiology, and effectively treat and prevent thrombotic and bleeding disorders.