Antithrombotic Properties Of A Low Molecular Weight Heparin

Abstract

The ability of heparin to prevent thrombosis has generally been assumed to be reflected by its anti-coagulant activity as measured with clotting assays such as the APTT. Recent clinical studies, however, using a low molecular weight heparin analogue, suggested that this is not necessarily always the case. The analogue had antithrombotic effect although the clotting time was only slightly affected. The present study was undertaken in order to further test this possibility in experimental animals using a low molecular weight heparin fragment with a high relative potency for inhibition of factor Xa. The heparin fragment was obtained after chemical degradation and chromatography on a antithrombin III gel. The molecular weight was 3000-4000 and the specific activity 150 U/mg and 20 U/mg as measured with an anti-Xa based assay and APTT, respectively. The fragment was tested and compared with normal mucosal heparin (corresponding activities 160 U/mg and 165 U/mg) in a rabbit thrombus model as described by Wessler. The method is based on intravenous injection of glas-activated human plasma which induces a transient hypercoagulable state during which a massive thrombus develops in stagnant blood. Thrombus formation were initiated 15 or 30 min after intravenous injection of the different heparins. Two doses, 30 and 60 U/kg (anti-Xa) of both the fragment and ordinary heparin were tested, and the results showed that the fragment was equipotent to heparin in preventing thrombus formation. However, the clotting time as measured with APTT was not significantly prolonged in rabbits treated with the fragment while a two-four fold prolongation was obtained in rabbits treated with ordinary heparin.