The biochemical properties of the non-vitamin K antagonist oral anticoagulants (NOACs) and their differences from the mechanism of action of vitamin K antagonists contribute to their properties as anticoagulants. These properties include as follows: (1) Inhibiting a single protease is much less effective at inhibiting coagulation than is inhibiting at multiple steps. Thus, the dose-response relationship between NOAC level and intensity of anticoagulation is shallower and more linear than that of vitamin K antagonists. This partially accounts for the greater safety of NOACs than vitamin K antagonists reported in some studies. (2) Because they are small molecules, NOACs can reach their target proteases in locations that plasma protease inhibitors, such as antithrombin, cannot. (3) NOACs compete with substrates for binding at the active site of the target protease and that binding is reversible. When the drug level falls, the drug dissociates from its target, and protease activity is restored. Thus, there is the possibility of a rebound in procoagulant activity if the drug is abruptly terminated. (4) The effects of a NOAC can be overcome by increasing the amount of substrate available for the target protease or the amount of protease produced. This property may contribute to the safety of NOACs and their potential reversibility by coagulation factor concentrates. The biochemical properties of NOACs contribute to their suitability for use in conditions that require a predictable moderate degree of anticoagulation when administered orally at a consistent dose. Their effects can be overcome by a sufficiently strong procoagulant stimulus. This characteristic likely contributes to their generally reduced risk of serious bleeding. However, they are not well suited for use in settings that require a profound degree of anticoagulation.

中文翻译：

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从基础科学角度看非维生素K拮抗剂口服抗凝剂的影响。

非维生素K拮抗剂口服抗凝剂（NOAC）的生化特性及其与维生素K拮抗剂作用机理的差异有助于其作为抗凝剂的特性。这些特性包括：（1）与在多个步骤中抑制相比，抑制单一蛋白酶的抑制凝血作用要差得多。因此，与维生素K拮抗剂相比，NOAC水平和抗凝强度之间的剂量反应关系更浅，更线性。这部分解释了NOACs的安全性高于某些研究中报道的维生素K拮抗剂。（2）由于NOAC分子很小，因此可以在血浆蛋白酶抑制剂（例如抗凝血酶）无法到达的位置到达其目标蛋白酶。（3）NOAC与底物竞争在靶蛋白酶活性位点的结合，并且该结合是可逆的。当药物水平下降时，药物与其靶标解离，并且蛋白酶活性得以恢复。因此，如果药物突然终止，则促凝活性可能反弹。（4）通过增加可用于靶蛋白酶的底物的量或产生的蛋白酶的量可以克服NOAC的作用。此性质可能有助于NOAC的安全性，以及浓缩凝血因子浓缩物的潜在可逆性。NOAC的生化特性有助于使其适合以恒定剂量口服时需要可预测的中等程度的抗凝作用。它们的作用可以通过足够强的促凝血刺激来克服。该特征可能有助于其普遍减少的严重出血风险。但是，它们不适用于需要高度抗凝作用的环境。