The Tissue Factor Pathway: How It Has Become a “Prima Ballerina”
The Tissue Factor Pathway: How It Has Become a “Prima Ballerina”
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DOI：
10.1055/s-0038-1642646
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发表时间：
1995-07
影响因子：
6.7
通讯作者：
S. Rapaport;L. Rao
中科院分区：
文献类型：
--
作者：
S. Rapaport;L. Rao
在1905年出版的一本历史性专著（1）（并于1958年翻译成英文（2））中，保罗·莫拉维茨总结了19世纪的实验，这些实验导致了涉及四种因素相互作用的凝血理论。其中三种存在于血浆凝血酶原、钙离子和纤维蛋白原中，但第四种是血栓激酶（今天称为促凝血酶原激酶，或更常见的组织因子（TF）），据信包含在血小板和白细胞中。当血液与组织或其他表面等非异物接触时，血小板和白细胞被认为会凝集并释放TF。释放的TF然后在钙离子存在下与凝血酶原反应以产生凝血酶，凝血酶将纤维蛋白原转化为血凝块的纤维蛋白链。被破坏的组织细胞被假定为TF的第二来源，这导致血液在伤口部位更快地凝结。到了世纪中期，随着新的凝血因子相继被发现，人们清楚地认识到血液凝固至少可以通过两种方式启动。如Morawitz所述，第一个是血液暴露于TF，TF现在已被鉴定为在血管内和周围的成纤维细胞表面上以及在策略性地位于全身的各种其他基质和组织细胞上组成性表达的糖蛋白，以防止组织损伤后的出血（3-5）。第二种是将血液在体外暴露于带负电荷的表面（如玻璃），其不是通过释放TF而是通过激活血浆蛋白因子XII（Hageman因子）来触发凝血（6）。到1955年，牛津大学的研究人员提出了独立途径的概念，即依赖于TF的“外在”途径和不依赖于TF-的“内在”途径，以产生凝血酶（Bergsagel，Waaler引用（7））。这一概念源于对两个观察结果的分析。第一，如描述一期凝血酶原时间试验的论文中所报告的（8），血友病患者的凝血酶原时间正常。向血浆中加入高浓度的TF不仅绕过了血友病A的凝血缺陷，即因子VIII缺乏，而且还绕过了当时新认识的血友病B的凝血缺陷，即因子IX缺乏。第二个观察结果是，患有罕见的遗传性疾病--凝血因子VII缺乏症的患者，凝血酶原时间明显延长，但他们的
In a historic monograph published in 1905 (1) (and translated into English in 1958 (2)), Paul Morawitz summarized the experiments of the 19th century that led to a theory of blood coagulation that involved the interaction of four factors. Three were present in plasma prothrombin, calcium ions and fibrinogen but the fourth, thrombokinase (today referred to as thromboplastin or, more commonly, as tissue factor (TF)), was believed to be contained within the platelets and leukocytes. When blood came into contact with wettable foreign matter like tissues or other surfaces, platelets and leukocytes were thought to agglutinate and liberate TF. The released TF then reacted with prothrombin in the presence of calcium ions to generate thrombin, which converted fibrinogen into the fibrin strands of the blood clot. Destroyed tissue cells were postulated to provide a second source of TF, which caused the blood to clot more rapidly at a wound site. By the middle years of the century as, one after another, new clotting factors were discovered, it became clear that blood coagulation could be initiated in at least two ways. The first was, as Morawitz had stated, the exposure of blood to TF, which has now been identified as a glycoprotein constitutively expressed on the surface of fibroblasts within and around blood vessels and on a variety o f other stromal and tissue cells strategically located throughout the body to protect against hemorrhage after tissue injury (3-5). The second was exposure of blood in vitro to a negatively charged surface such as glass, which triggers coagulation not by releasing TF but by activating the plasma protein, factor XII (Hageman factor) (6). By 1955 investigators at Oxford had advanced the concept of separate pathways an “extrinsic” pathway dependent upon TF and an “intrinsic” pathway independent o fT F -to the generation of thrombin (Bergsagel, quoted by Waaler (7)). This concept stemmed from an analysis of two observations. The first, as reported in the paper describing the one-stage prothrombin time test (8), was that patients with hemophilia had a normal prothrombin time. Adding a high concentration of TF to plasma bypassed not only the clotting defect of hemophilia A, factor VIII deficiency, but also the clotting defect of the then newly recognized hemophilia B, factor IX deficiency. The second observation was that patients with a much rarer hereditary disorder, factor VII deficiency, had a markedly prolonged prothrombin time yet their