Pangrazzi J, Abbadini M, Zametta M, Naggi A, Torri G, Casu B, Donati M B
Biochem Pharmacol. 1985 Sep 15;34(18):3305-8. doi: 10.1016/0006-2952(85)90350-8.
Low molecular weight (LMW) heparin prevents venous thrombosis by potentiating the inhibition of coagulation factor Xa. Heparin, however, has other biological properties whose role in the prevention of thrombosis is still unknown. The aim of our study was to compare the antithrombotic activity of a LMW heparin and its parent molecule in an attempt to understand better the mechanism and structural requirements for heparin's antithrombotic effect. We studied a preparation of an unfractionated pig mucosal heparin pure by any accepted criteria (electrophoresis in various systems, conductimetric titration and NMR spectra) and a LMW heparin fraction obtained from the former by fractional precipitation with ethanol. Both heparins completely prevented thrombus formation in an experimental model of stasis-induced venous thrombosis in rats. When administered intravenously to rats, the unfractionated heparin had an ex vivo anti-Xa/APTT ratio of 1.67, versus 6.60 of the LMW heparin fraction. Unexpectedly, both heparins induced a significant prolongation of tail bleeding time, performed by two different techniques, the "transection" (mostly exploring blood clotting) and the "template" (exploring the platelet/vessel wall interactions). This study suggests that, beside anticoagulation, other effects may play a role in both the antithrombotic and haemorrhagic effects of some heparins and LMW heparin fractions.
低分子量（LMW）肝素通过增强对凝血因子Xa的抑制作用来预防静脉血栓形成。然而，肝素还具有其他生物学特性，其在预防血栓形成中的作用仍不明确。我们研究的目的是比较一种低分子量肝素及其母体分子的抗血栓活性，以更好地理解肝素抗血栓作用的机制和结构要求。我们研究了一种根据任何公认标准（在各种系统中进行电泳、电导滴定和核磁共振光谱）均为纯品的未分级猪黏膜肝素制剂，以及通过用乙醇分级沉淀从前者获得的一种低分子量肝素级分。在大鼠淤滞诱导的静脉血栓形成实验模型中，两种肝素均能完全预防血栓形成。当静脉注射给大鼠时，未分级肝素的体外抗Xa/活化部分凝血活酶时间（APTT）比值为1.67，而低分子量肝素级分为6.60。出乎意料的是，两种肝素均通过两种不同技术，即“横切”（主要检测血液凝固）和“模板”（检测血小板/血管壁相互作用），显著延长了尾部出血时间。这项研究表明，除了抗凝作用外，其他效应可能在某些肝素和低分子量肝素级分的抗血栓和出血作用中发挥作用。
