Studies in Man and Experimental Animals of a Low Molecular Weight Heparin Fraction

Abstract

SummaryIn vitro and in vivo studies were carried out on a commercially prepared low molecular weight heparin fraction. By APTT assay the fraction had a specific activity of half that of unfractionated mucosal heparin, yet retained full potency by anti-Xa assay (both clotting and chromogenic substrate). When administered intravenously to human volunteers, the anti-Xa/APTT ratio remained the same as it was in vitro. However, after subcutaneous injection, the ratio increased and anti-Xa activity could not be fully neutralized ex vivo by PF4. The fraction was as effective as unfractionated heparin in preventing experimental serum-induced thrombosis, suggesting that a heparin fraction with high specific activity by anti-Factor Xa assay compared to APTT activity may be an effective drug for the prophylaxis of venous thrombosis.

Subcutaneous Heparin Treatment of Deep Venous Thrombosis: A Comparison of Unfractionated and Low Molecular Weight Heparin

“…In animal experiments, LH has proved as effective as UH in preventing thrombosis [6][7][8], Animal experiments have also suggested that the bleeding risk using LH is reduced compared to UH [7,8], Further more, LH seems less prone to induce platelet aggregation [9] and lipase activity [10]. Sub cutaneous administration of LH is effective in the prevention of DVT [11], but bleeding is still a potential hazard [12], Increased halflife and improved bioavailability [13,14] of LH as compared to UH suggest that LH is particularly suitable for subcutaneous ad ministration.…”

Relationship between Biological Activity and Concentration of a Low-Molecular-Weight Heparin (PK 10169) and Unfractionated Heparin after Intravenous and Subcutaneous Administration

“…Low-molecular-weight (LMW) heparins strongly inhibit factor Xa [12,15], but have relatively little activity either in anti-Ila as says or in tests of overall anticoagulant activ ity such as the activated partial thromboplas tin time. Nevertheless, they are effective anti thrombotic agents [11].…”

Whither Thromboprophylaxis After Total Hip Replacement?

“…In animal models low concentrations of heparin have been shown to be highly effective in preventing stasis thrombosis. 28 This has now been amply confirmed by numerous clinical trials. The advent of LMWH, in terms of effectiveness, ease of use, and minimal risk, represents an important therapeutic advance in achieving effective prophylaxis throughout the period of maximum risk after major surgery.…”