Zammit A, Dawes J
Heart Research Institute, Sydney, Australia.
Thromb Haemost. 1994 Jun;71(6):759-67.
Orgaran is a LMW heparinoid composed of heparan sulphate (83% w/w) of which 4-5% has high affinity for antithrombin, dermatan sulphate (12% w/w) and chondroitin sulphate (5% w/w). To examine the contribution of the low-affinity fraction to Orgaran's antithrombotic activity we have quantitated the binding of plasma proteins to Orgaran and its component fractions in whole, hirudin-anticoagulated human plasma. Antithrombin, largely bound to the high-affinity fraction, and histidine-rich glycoprotein, interacting with low-affinity components, were the dominant proteins bound to Orgaran. Vitronectin, fibrinogen, fibronectin, heparin cofactor II, and apolipoprotein B were also detected in small amounts. The ratio of bound antithrombin, histidine-rich glycoprotein and vitronectin to GAG was negatively correlated with the Orgaran concentration in plasma, implying that the efficacy of Orgaran may not be linearly related to dose. Binding of antithrombin to the high-affinity fraction was not decreased by other plasma proteins or affected by addition of low-affinity material. Moreover, the antithrombin and anti-factor Xa activities of the high-affinity material were unaltered by low-affinity GAGs. On the basis of our results we conclude that the low-affinity material does not contribute to the antithrombotic activity of Orgaran by binding non-anticoagulant plasma proteins and releasing the high-affinity chains to interact with antithrombin and its target proteinases.
奥加诺（Orgaran）是一种低分子量类肝素，由硫酸乙酰肝素（83% w/w）、硫酸皮肤素（12% w/w）和硫酸软骨素（5% w/w）组成，其中4 - 5%的硫酸乙酰肝素对抗凝血酶具有高亲和力。为了研究低亲和力部分对奥加诺抗血栓活性的贡献，我们在水蛭素抗凝的人全血浆中定量了血浆蛋白与奥加诺及其组成部分的结合情况。抗凝血酶主要与高亲和力部分结合，富含组氨酸糖蛋白与低亲和力成分相互作用，它们是与奥加诺结合的主要蛋白质。此外，还检测到少量的玻连蛋白、纤维蛋白原、纤连蛋白、肝素辅因子II和载脂蛋白B。结合的抗凝血酶、富含组氨酸糖蛋白和玻连蛋白与糖胺聚糖的比例与血浆中奥加诺的浓度呈负相关，这意味着奥加诺的疗效可能与剂量并非线性相关。其他血浆蛋白不会降低抗凝血酶与高亲和力部分的结合，添加低亲和力物质也不会影响这种结合。此外，低亲和力糖胺聚糖不会改变高亲和力物质的抗凝血酶和抗Xa因子活性。基于我们的研究结果，我们得出结论：低亲和力物质不会通过结合非抗凝血浆蛋白并释放高亲和力链以与抗凝血酶及其靶蛋白酶相互作用来对奥加诺的抗血栓活性产生贡献。
