Heparin fractions with high and low affinities to antithrombin III are cleared at different rates.
The clearance characteristics of standard heparin (SH) and its fractions with high and low affinity to antithrombin III (HAH and LAH respectively) were studied by injecting 125I-labelled SH, HAH and LAH intravenously into the rabbits in increasing doses. Serial blood samples were then collected from an indwelling cannula for measurement of clearance, based both on radioactivity and anticoagulant activity. For equivalent weights injected, the radioactivity of HAH was cleared more slowly from the circulation than that of either SH or LAH. The radioactivity of SH, in turn, was cleared more slowly than that of LAH. The clearance of HAH, measured both by radioactivity and by anticoagulant activity were similar, whereas the clearance of the radioactivity of SH was more rapid than its anticoagulant activity (i.e. anti-factor Xa activity). These observations suggest that the radioactivity clearance curves of SH reflect a "net" estimation of the more complex clearance curves of the different heparin moieties whereas the anticoagulant clearance curves of SH reflects the clearance of the anticoagulant activity of a specific heparin fraction, in this case, the clearance of the anti-factor Xa activity of HAH. These differences suggest that the HAH:LAH ratio is, at any given time, greater in vivo than the same ratio measured in vitro.
D000818:Animals; D000990:Antithrombin III / Q000378:metabolism / Q000502:physiology*; D005170:Factor X / Q000037:antagonists & inhibitors; D015951:Factor Xa; D005260:Female; D006493:Heparin / Q000008:administration & dosage / Q000378:metabolism* / Q000494:pharmacology; D007275:Injections, Intravenous; D007457:Iodine Radioisotopes; D007700:Kinetics; D008297:Male; D008657:Metabolic Clearance Rate; D011817:Rabbits; D013997:Time Factors
D007457:Iodine Radioisotopes; D000990:Antithrombin III; D005170:Factor X; D006493:Heparin; D015951:Factor Xa