Pharmacologic Profile of a Low-Molecular-Weight Heparin Depolymerized by γ-Irradiation

Abstract

Low molecular weight heparins (LMWHs) are considered to be the agent of choice for the prophylaxis of DVT in medical and surgical patients. Conventionally, these agents have been produced by fractionation of or by chemical or enzymatic depolymerization of native heparin. The fractionated heparin retains many of its biological properties such as AT III affinity and sulfate content. γ-irradiation (⁶⁰Co) has been used to depolymerize GAGs (De Ambrosi et al. In: Biomedical and Biotechnological Advances in Industrial Polysaccharides, pp. 45-53). This procedure has now been used for the preparation of LMWH derivatives of varying molecular weight. The current studies examine the biochemical and pharmacologic profile of one such γ-irradiated depolymerized heparin. In standard clotting and amidolytic antiprotease assays (PT, APTT, AXa, Alla), γ-irradiated depolymerized heparin produced equal or stronger activity when compared to a LMWH produced by nitrous acid depolymerization and retained the ability to activate AT III and HCII. Initial results indicate that LMWHs produced by γ-irradiation exhibit comparable antithrombotic actions to those produced by chemical depolymerization when measured in animal models of thrombosis. γ-Irradiation may be a useful method for the production of LMWHs.

Key words:

Heparin - LMW heparin - anticoagulants - serpins - antithrombotic agents