Summary
It is widely reported that persistent anti-Xa activity follows administration of low
molecular weight heparins. To identify the effectors of this activity we have injected
125I-labelled Enoxaparin sodium into rabbits and subsequently analysed the circulating
radiolabelled material and anti-Xa activity by affinity and size exclusion chromatography.
Antithrombin III-binding material derived from the injected drug was responsible for
all the anti-Xa amidolytic activity. At early times after injection additional anticoagulant
activity which was largely attributable to tissue factor pathway inhibitor was measured
by the Heptest clotting assay after removal of glycosaminoglycans from plasma samples.
Small radiolabelled fragments, including penta/hexasaccharide with affinity for antithrombin
III, were detectable in the circulation 1 week later, and sulphated oligosaccharides
persisted for 3-4 weeks. Significant quantities of radiolabel remained in the liver
and kidney several weeks post-injection; these organs may sequester some of the injected
drug and give rise to circulating biologically active material by degradation and
secretion of catabolic products into the plasma.