What is all that thrombin for?
What is all that thrombin for?
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DOI：
10.1046/j.1538-7836.2003.00298.x
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发表时间：
2003-07-01
影响因子：
10.4
通讯作者：
Butenas, S
中科院分区：
文献类型：
--
作者：
Mann, KG;Brummel, K;Butenas, S
由组织因子暴露于血液引发的止血过程是在两个不同阶段发生的阈值限制反应。在起始阶段，产生少量的因子（F）Xa、FIXa和凝血酶。后者将原辅因子FV和FVIII活化为活化的辅因子，所述活化的辅因子与它们的伴随丝氨酸蛋白酶一起形成内在FX活化剂（FVIIIa-FIXa）和凝血酶原酶（FVa-FXa），所述内在FX活化剂和凝血酶原酶在增殖阶段期间产生大量FXa和凝血酶。凝血过程（纤维蛋白形成）发生在增殖阶段的开始，此时仅产生5-10 nM凝血酶。因此，绝大多数（大于95%）凝血酶是在凝血酶生成的增殖阶段凝血后产生的。患有血友病A或血友病B的个体的血液没有能力产生内源性FXase，因此不能支持反应的增殖阶段。由于基于凝块的检测在传播阶段之前结束，因此其对血友病A和B不敏感。凝血酶生成的传播阶段的开始和大小受到与血栓形成和出血性疾病相关的遗传多态性、健康个体中促凝血剂和抗凝剂的天然丰度以及影响血栓形成病理学的药理学干预的影响。因此，我们怀疑凝血酶生成的整个过程（从反应的起始到增殖和终止阶段）的性能与出血和血栓形成病理学相关。
The hemostatic process initiated by the exposure of tissue factor to blood is a threshold limited reaction which occurs in two distinct phases. During an initiationphase, small amounts of factor (F)Xa, FIXa and thrombin are generated. The latter activates the procofactors FV and FVIII to the activated cofactors which together with their companion serine proteases form the intrinsic FX activator (FVIIIa-FIXa) and prothrombinase (FVa-FXa) which generate the bulk of FXa and thrombin during a propagation phase. The clotting process (fibrin formation) occurs at the inception of the propagation phase when only 5-10 nM thrombin has been produced. Consequently, the vast majority (greater than 95%) of thrombin is produced after clotting during the propagation phase of thrombin generation. The blood of individuals with either hemophilia A or hemophilia B has no ability to generate the intrinsic FXase, and hence is unable to support the propagation phase of the reaction. Since clot based assays conclude before the propagation phase they are not sensitive to hemophilia A and B. The inception and magnitude of the propagation phase of thrombin generation is influenced by genetic polymorphisms associated with thrombotic and hemorrhagic disease, by the natural abundance of pro- and anticoagulants in healthy individuals and by pharmacologic interventions which influence thrombotic pathology. Therefore, it is our suspicion that the performance of the entire process of thrombin generation from initiation through propagation and termination phases of the reaction are relevant with respect to both hemorrhagic and thrombotic pathology.