Béguin S, Choay J, Hemker H C
Department of Biochemistry, University of Limburg, Maastricht, The Netherlands.
Thromb Haemost. 1989 Jun 30;61(3):397-401.
We investigated the effect on thrombin generation in plasma of the pentasaccharide that represent the AT III/binding site in heparin. This compound has no effect on the breakdown of thrombin in plasma. It dose-dependently inhibits the formation of thrombin in both the intrinsic and the extrinsic pathway. If coagulation is triggered by the complete prothrombinase complex (phospholipid--factor Va--factor Xa) under conditions in which the large majority of factor Xa is bound to the complex, the inhibition of prothrombinase activity is only minor. If no factor Va is present or if the prothrombinase activity is triggered by adding complete tenase (PL-FVIIIa-FIXa) or incomplete tenase (PL-FIXa) to the plasma the inhibition by pentasaccharide is of the same magnitude as that in the intrinsic or extrinsic system. We conclude that the pentasaccharide inhibits blood coagulation by catalysing the inactivation of free factor Xa. In contrast to classical heparin it does inhibit the peak of thrombin formation in platelet rich plasma, probably because it is less subject to inactivation by heparin binding proteins from platelets than classical heparin is.
我们研究了代表肝素中抗凝血酶III结合位点的五糖对血浆中凝血酶生成的影响。该化合物对血浆中凝血酶的降解没有作用。它在剂量依赖的情况下抑制内源性和外源性途径中凝血酶的形成。如果在绝大多数因子Xa与复合物结合的条件下，由完整的凝血酶原酶复合物（磷脂-因子Va-因子Xa）触发凝血，凝血酶原酶活性的抑制作用很小。如果不存在因子Va，或者通过向血浆中添加完整的内源性凝血活酶（磷脂-因子VIIIa-因子IXa）或不完整的内源性凝血活酶（磷脂-因子IXa）来触发凝血酶原酶活性，五糖的抑制作用与在内源性或外源性系统中的抑制作用相同。我们得出结论，五糖通过催化游离因子Xa的失活来抑制血液凝固。与传统肝素不同，它确实抑制富含血小板血浆中凝血酶形成的峰值，这可能是因为它比传统肝素更不容易被来自血小板的肝素结合蛋白灭活。
