Current concepts of hemostasis: implications for therapy.
Current concepts of hemostasis: implications for therapy.
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当前止血的概念：对治疗的影响。
DOI：
10.1097/00000542-200403000-00036
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发表时间：
2004
期刊：
影响因子：
8.8
通讯作者：
Escobar,MiguelA
中科院分区：
文献类型：
--
作者：
Roberts,HaroldR;Monroe,DougaldM;Escobar,MiguelA
早在1964年，就有人提出导致止血的凝血反应按顺序步骤发生，其中酶原凝血因子在被激活时能够以瀑布或级联机制激活随后的凝血因子。1因子XII被表面如胶原蛋白激活，产生因子XIIa，然后因子XIIa能够将因子XI激活为XIa，然后依次激活其他凝血因子，最终导致凝血酶原快速转化为凝血酶。后来，当发现以前被认为是酶的凝血因子实际上是辅因子时，这一概念被修改了。例如，发现因子VIII是因子IX的辅因子，而因子V是因子X的辅因子（图1）。那些接受凝血概念的人设想了凝血的内在和外在途径。内源性系统完全由循环血液中的因子组成，而外源性途径包括组织因子（TF），被认为是循环的外源性，并作为因子VII的受体。这一概念认为，因子X可以通过内源性和外源性途径激活。然而，人们很早就意识到，外在和内在系统并不是相互独立的。已知因子XII、前激肽释放酶和高分子量激肽原的缺乏与出血无关。此外，因子VIII和IX的缺陷没有得到补偿的一个完整的外源性系统，也不是一个完整的内源性途径减轻因子VII的缺陷。最终，人们认识到TF/VIIa复合物可以激活因子IX和X，这表明外源性和内源性途径的概念不适用于体内止血，尽管该概念对于诊断目的是有价值的方案。后者作为载体分子，通过与血管性血友病因子的结合将因子VIII从循环中转运到血小板表面。vonWillebrand因子也在血小板粘附于血管壁组分中起作用。
AS early as 1964, it was proposed that coagulation reactions leading to hemostasis occurred in sequential steps in which a zymogen clotting factor, when activated, was capable of activating subsequent clotting factors in a waterfall or cascade mechanism. 1 Factor XII was activated by a surface, such as collagen, leading to factor XIIa, which then was capable of activating factor XI to XIa and thereafter to sequential activation of the other clotting factors, finally leading to the rapid conversion of prothrombin to thrombin. Later, this concept was modified when it was found that clotting factors previously thought to be enzymes were in fact cofactors. For example, factor VIII was found to be a cofactor for factor IX, and factor V was found to be a cofactor for factor X (fig. 1). Those who accepted this concept of coagulation envisioned intrinsic and extrinsic pathways of coagulation. The intrinsic system was composed entirely of factors in the circulating blood, whereas the extrinsic pathway included tissue factor (TF), thought to be extrinsic to the circulation and which acted as a receptor for factor VII. This concept held that factor X could be activated by both the intrinsic and extrinsic pathways. However, it was realized early on that the extrinsic and intrinsic systems were not independent of one another. It was known that deficiency of factor XII, prekallikrein, and high-molecular-weight kininogen were not associated with bleeding. Furthermore, deficiencies of factors VIII and IX were not compensated for by an intact extrinsic system, neither was a deficiency of factor VII alleviated by an intact intrinsic pathway. Ultimately, it was realized that the TF/VIIa complex could activate both factors IX and X, suggesting that the extrinsic and intrinsic pathway concept was not applicable to in vivo hemostasis, though the concept was a valuable scheme for diagnostic purposes.Although not shown in figure 1, it is now known that factor VIII circulates in complex with von Willebrand factor, the latter acting as a carrier molecule that serves to transport factor VIII from circulation to the platelet surface by virtue of the binding of von Willebrand factor. von Willebrand factor also plays a role in the adhesion of platelets to components of the vessel wall.