[Antithrombotic effects of low molecular weight heparin (FR-860) in rabbits]

Effects of low molecular weight heparin (FR-860) were investigated on the arterio-venous (A-V) shunt model and on the in vitro blood coagulation system compared to conventional unfractionated heparin (UF-heparin) in rabbits. In the A-V shunt model, FR-860 (12.5-50 U/kg, i.v.) and UF-heparin (25 and 50 U/kg, i.v.) dose-related inhibited thrombotic formation in the tube of the A-V shunt at 30 min after starting blood circulation. Both FR-860 and UF-heparin dose-relatedly increased the anti-F.Xa activity at 5 min after starting blood circulation. However, FR-860 showed weaker effects in a prolongation of the aPTT, PT and thrombin time than UF-heparin in the A-V shunt model. Neither FR-860 nor UF-heparin had any influence on platelet aggregation. FR-860 also had a weaker effect in the prolongation of the plasma recalcification time, aPTT and PT than UF-heparin in vitro. FR-860 showed equipotent efficacy on the anti-F.Xa activity and had weak anti-thrombin activity compared to that of UF-heparin in vitro. These results suggest that the antithrombotic effect of FR-860 mainly depends on its anti-F.Xa activity but not on the antithrombin activity. Therefore, FR-860 is more efficient and lower in bleeding risk than UF-heparin in hemodialysis and thrombotic disorders.