低分子量肝素的抗Xa因子和抗IIa因子活性对凝血酶生成各阶段的影响。
Effect of the anti-factor Xa and anti-factor IIa activities of low-molecular-weight heparins upon the phases of thrombin generation.
作者信息
Gerotziafas G T, Petropoulou A D, Verdy E, Samama M M, Elalamy I
机构信息
Service d'Hématologie Biologique, Hôpital Tenon, Assistance Publique Hôpitaux de Paris, Paris, France.
出版信息
J Thromb Haemost. 2007 May;5(5):955-62. doi: 10.1111/j.1538-7836.2007.02477.x.
BACKGROUND
Low-molecular-weight heparins (LMWHs), derived from unfractionated heparin (UFH) by different depolymerization procedures, vary in both their relative abilities to enhance the inhibition of FXa (anti-FXa) and thrombin (anti-FIIa), and in their physicochemical properties.
OBJECTIVE
We aimed to profile the inhibition of thrombin generation induced by bemiparin, enoxaparin, nadroparin, dalteparin and tinzaparin in platelet-rich plasma (PRP), and to compare them with UFH and fondaparinux (a synthetic pentasaccharide that specifically enhances FXa inhibition).
METHODS
Different LMWHs, UFH or fondaparinux were added to normal PRP. Thereafter, tissue factor-triggered thrombin generation was assessed using the Thrombogram-Thrombinoscope assay.
RESULTS
At equivalent anti-FIIa activity concentrations, LMWHs and UFH exhibited similar inhibitory effects upon thrombin generation. However, when used at equivalent anti-FXa activity concentrations, tinzaparin was significantly more active than the other LMWHs at inhibiting thrombin generation, and had similar activity to that of UFH. Enoxaparin, nadroparin and dalteparin all showed similar inhibitory activities. In these experiments, bemiparin exhibited the lowest inhibitory effect on thrombin generation of all the LMWHs. At 0.1 microg mL(-1) (0.093 anti-FXa IU mL(-1)), fondaparinux inhibited the rate of thrombin generation by 50%. A 7-fold higher concentration of fondaparinux was required to inhibit the endogenous thrombin potential by 50%.
CONCLUSIONS
LMWHs have a variable inhibitory effect on thrombin generation in vitro when compared by anti-FXa activity, but are similar when compared by their anti-FIIa activities. The rate of thrombin generation during the propagation phase, rather than the endogenous thrombin potential, is more sensitive to the anticoagulant activity of fondaparinux and the polysaccharide chains of LMWHs possessing only anti-FXa activity.
背景
低分子量肝素（LMWHs）是通过不同的解聚程序从普通肝素（UFH）衍生而来，其增强对因子Xa（抗FXa）和凝血酶（抗FIIa）抑制作用的相对能力以及理化性质各不相同。
目的
我们旨在分析贝米肝素、依诺肝素、那屈肝素、达肝素和替扎肝素在富血小板血浆（PRP）中对凝血酶生成的抑制情况，并将它们与UFH和磺达肝癸钠（一种特异性增强FXa抑制作用的合成五糖）进行比较。
方法
将不同的LMWHs、UFH或磺达肝癸钠添加到正常PRP中。此后，使用血栓图-凝血酶监测仪检测组织因子触发的凝血酶生成情况。
结果
在等效的抗FIIa活性浓度下，LMWHs和UFH对凝血酶生成表现出相似的抑制作用。然而，当以等效的抗FXa活性浓度使用时，替扎肝素在抑制凝血酶生成方面比其他LMWHs显著更具活性，并且与UFH具有相似的活性。依诺肝素、那屈肝素和达肝素均表现出相似的抑制活性。在这些实验中，贝米肝素在所有LMWHs中对凝血酶生成的抑制作用最低。在0.1μg mL⁻¹（0.093抗FXa IU mL⁻¹）时，磺达肝癸钠抑制凝血酶生成速率达50%。抑制内源性凝血酶潜力达50%则需要7倍浓度更高的磺达肝癸钠。
结论
通过抗FXa活性比较时，LMWHs在体外对凝血酶生成具有可变的抑制作用，但通过抗FIIa活性比较时则相似。在传播阶段的凝血酶生成速率，而非内源性凝血酶潜力，对磺达肝癸钠的抗凝活性以及仅具有抗FXa活性的LMWHs多糖链更为敏感。
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