Guerrero Belsy, López Mercedes
Invest Clin. 2015 Dec;56(4):432-54.
In the sixties, the clotting cascade was proposed, which describes the coagulation process as a sequence of enzymatic events initiated by two different pathways, the intrinsic and the extrinsic pathways, converging on a common pathway, to generate a multifunctional enzyme, thrombin, whose main function is to convert fibrinogen into fibrin, a protein that polymerizes spontaneously to form the building block of a hemostatic clot. Later, it was proposed a cell-based model of the hemostasis according to that coagulation does not occur as a consequence of linear sequential enzyme activation pathways, but rather via a network of simultaneous interactions between plasmatic and transmembrane proteins, as well as several cellular types, that allow the formation of highly efficient enzymatic complexes that lead to thrombin generation. In this review, we summarize these two approaches highlighting the functions of thrombin within the hemostasis and the inhibition mechanisms that regulate the blood coagulation. Moreover, we described different tests that are used to assess the function of the coagulation system, such as: activated partial thromboplastin time, prothrombin time, thrombin time, reptilase time, ecarin clotting time, and the use of chromogenic substrates to evaluate individual coagulation factors. Finally, because of thrombin generation is a fundamental part of the blood coagulation and, an estimation of how well a particular individual can generate thrombin may correlate with either a risk of bleeding or thrombosis, we also include the existing methods to evaluate the potential of thrombin generation in an individual.
在20世纪60年代,凝血级联反应被提出,它将凝血过程描述为由两条不同途径(内源性途径和外源性途径)启动的一系列酶促事件,这两条途径汇聚于一条共同途径,以产生一种多功能酶——凝血酶,其主要功能是将纤维蛋白原转化为纤维蛋白,纤维蛋白可自发聚合形成止血凝块的基本组成部分。后来,有人提出了一种基于细胞的止血模型,根据该模型,凝血并非由于线性顺序酶激活途径而发生,而是通过血浆蛋白和跨膜蛋白以及几种细胞类型之间同时相互作用的网络发生,这些相互作用允许形成高效的酶复合物,从而导致凝血酶生成。在这篇综述中,我们总结了这两种方法,突出了凝血酶在止血中的功能以及调节血液凝固的抑制机制。此外,我们描述了用于评估凝血系统功能的不同测试,例如:活化部分凝血活酶时间、凝血酶原时间、凝血酶时间、蝰蛇毒时间、蛇毒凝血时间,以及使用发色底物评估单个凝血因子。最后,由于凝血酶生成是血液凝固的一个基本部分,并且估计特定个体产生凝血酶的能力如何可能与出血或血栓形成风险相关,我们还包括了评估个体凝血酶生成潜力的现有方法。