FACTORS IXA AND XA PLAY DISTINCT ROLES IN TISSUE FACTOR-DEPENDENT INITIATION OF COAGULATION
FACTORS IXA AND XA PLAY DISTINCT ROLES IN TISSUE FACTOR-DEPENDENT INITIATION OF COAGULATION
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DOI：
10.1182/blood.v86.5.1794.bloodjournal8651794
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发表时间：
1995-09-01
期刊：
影响因子：
20.3
通讯作者：
ROBERTS, HR
中科院分区：
文献类型：
--
作者：
HOFFMAN, M;MONROE, DM;ROBERTS, HR
组织因子是凝血的主要起始因子。因子IX和因子X都被因子VIIa和组织因子（VIIa/TF）的复合物激活。本研究的目的是确定因子IXa和Xa在启动凝血中的具体作用。我们使用了由VIIa/TF启动的体外凝血模型系统，包括未活化的血小板和因子II、V、VIII、IX和X、组织因子途径抑制剂和抗凝血酶III的血浆浓度。在某些情况下，因子IX和/或因子X被携带组织因子的单核细胞活化，但在某些实验中，使用皮摩尔浓度的预活化因子IX或因子X来引发反应。测定定时样本的血小板活化和凝血酶活性。因子Xa在启动血小板活化方面的效力是因子IXa的10倍，但因子IXa在促进凝血酶生成方面比因子Xa有效得多。在存在VIIa/TF的情况下，血小板活化和凝血酶生成都需要因子X，而因子IX仅需要凝血酶生成。我们得出结论，VIIa/TF-激活因子IXa和Xa具有不同的生理作用。最初被VIIa/TF激活的因子Xa的主要作用是通过在血小板附近产生最初的少量凝血酶来激活血小板。另一方面，因子IXa通过在血小板表面提供因子Xa来增强凝血酶生成，导致凝血酶原酶形成。只有极少量的因子IX和X需要被VIIa/TF激活来执行这些不同的功能。我们的实验表明，启动凝血是高度依赖于激活少量的因子IXa和Xa在血小板表面附近，这些因素在随后的事件中发挥不同的作用，导致爆炸的凝血酶生成。此外，由VIIa/TF产生的因子IXa和Xa的特定作用不一定由因子IXa和Xa产生的动力学反映。(C)1995年，美国血液学会。
Tissue factor is the major initiator of coagulation. Both factor IX and factor X are activated by the complex of factor VIIa and tissue factor (VIIa/TF). The goal of this study was to determine the specific roles of factors IXa and Xa in initiating coagulation. We used a model system of in vitro coagulation initiated by VIIa/TF and that included unactivated platelets and plasma concentrations of factors II, V, VIII, IX, and X, tissue factor pathway inhibitor, and antithrombin III. In some cases, factor IX and/or factor X were activated by tissue factor-bearing monocytes, but in some experiments, picomolar concentrations of preactivated factor IX or factor X were used to initiate the reactions. Timed samples were assayed for both platelet activation and thrombin activity. Factor Xa was 10 times more potent than factor IXa in initiating platelet activation, but factor IXa was much more effective in promoting thrombin generation than was factor Xa. In the presence of VIIa/TF, factor X was required for both platelet activation and thrombin generation, while factor IX was only required for thrombin generation. We conclude that VIIa/TF-activated factors IXa and Xa have distinct physiologic roles. The main role of factor Xa that is initially activated by VIIa/TF is to activate platelets by generating an initial, small amount of thrombin in the vicinity of platelets. Factor IXa, on the other hand, enhances thrombin generation by providing factor Xa on the platelet surface, leading to prothrombinase formation. Only tiny amounts of factors IX and X need to be activated by VIIa/TF to perform these distinct functions. Our experiments show that initiation of coagulation is highly dependent on activation of small amounts of factors IXa and Xa in proximity to platelet surfaces and that these factors play distinct roles in subsequent events, leading to an explosion of thrombin generation. Furthermore, the specific roles of factors IXa and Xa generated by VIIa/TF are not necessarily reflected by the kinetics of factor IXa and Xa generation. (C) 1995 by The American Society of Hematology.