title: Low affinity heparin is an antithrombotic agent.
abstract: We have investigated the antithrombotic activities and haemorrhagic side effects of a low affinity heparin (LAH). In the rabbit thrombosis model using activated human serum as the thrombogenic challenge, the effect of LAH on 10' and 20' stasis was studied. At 10' stasis, 150 micrograms/kg of LAH reduced thrombus formation by 67% and total prevention was achieved at 500 micrograms/kg. At 20' stasis, 150 micrograms/kg was totally ineffective, 500 micrograms/kg was partially effective and 1000 micrograms/kg was required to achieve complete prevention of thrombosis. Mean peak circulatory level following infusion of 500 micrograms/kg of LAH was found to be 1.6 micrograms/ml by heparin cofactor II based assay and 0.13 iu/ml by anti-factor Xa assay. Thrombin generation tests of the same post injection samples showed an 80% reduction in thrombin production when compared with pre-injection samples. At 2.5 mg/kg, the mean bleeding time ratio (challenge:control) measured in the rabbit ear template model was 1.25 (cf saline control 0.88). Compared with results from previous studies on unfractionated heparin and dermatan sulphate, LAH is approximately 6 times less effective than UFH but 5 times more potent than dermatan sulphate. Since the mean bleeding time for UFH at 2.5 mg/kg was previously found to increase nearly two fold over the control value, LAH may present a lesser haemorrhagic risk than UFH. These data suggest that LAH is more effective in directly preventing venous thrombosis than dermatan sulphate. Although LAH is not as effective as UFH on a weight basis in the impairment of thrombogenesis, it may carry significantly lower bleeding risk.
authors.affiliation: National Institute for Biological Standards and Control, Potters Bar, Hertfordshire, UK.
authors.forename: E
authors.initials: E
authors.lastname: Gray
authors.forename: S
authors.initials: S
authors.lastname: Cesmeli
authors.forename: J C
authors.initials: JC
authors.lastname: Lormeau
authors.forename: A B
authors.initials: AB
authors.lastname: Davies
authors.forename: D A
authors.initials: DA
authors.lastname: Lane
mesh_terms: D000818:Animals; D001760:Bleeding Time; D003871:Dermatan Sulfate / Q000494:pharmacology / Q000633:toxicity; D004195:Disease Models, Animal; D006470:Hemorrhage / Q000139:chemically induced; D006493:Heparin / Q000097:blood / Q000494:pharmacology* / Q000633:toxicity; D006801:Humans; D008657:Metabolic Clearance Rate; D011817:Rabbits; D013917:Thrombin / Q000096:biosynthesis; D013924:Thrombophlebitis / Q000517:prevention & control*
chemical_list: D003871:Dermatan Sulfate; D006493:Heparin; D013917:Thrombin