A Comparative Study Of Heparin And Heparin Fractions In Preventing Experimental Venous Thrombosis

We have compared the relative efficacy in preventing venous thrombosis of an ordinary mucosal heparin, a low molecular weight (LMW) heparin fraction and a decasaccharide fragment with high affinity for AT III. We examined the extent to which all three preparations impaired the formation of serum-induced stasis thrombi in New Zealand White rabbits. The LMW fraction, despite having an in vitro potency by APTT half that of ordinary heparin (but comparable anti-Xa activity) was as effective as heparin on a weight basis in preventing thrombosis.

Two minutes after intravenous injection of 30 μg/kg of the LMW fraction the mean blood level by anti-Xa clotting assay was 0.12 i.u./ml (range 0.08-0.21), which was sufficient to prevent thrombosis. In contrast, the decasaccharide fragment, which had a specific activity in vitro by anti-Xa assays of 1000-1300 i.u./mg, but essentially no activity by APTT or thrombin time assays, prevented stasis thrombi only when given at a dose of 100 μg/kg, giving blood levels in excess of 0.3 i.u./ml by anti-Xa assays.

It is concluded that in this experimental model a decasaccharide fragment, despite having a very high affinity for AT III, was less effective on a weight for weight basis than either ordinary heparin or a LMW fraction in preventing venous thrombosis. This suggests that while a sufficiently high anti-Xa activity can alone prevent venous thrombosis, the effectiveness of heparin as an antithrombotic drug does not depend solely on its AT III-binding capacity.