THE RELATIONSHIP BETWEEN THE HEMORRHAGIC AND ANTITHROMBOTIC PROPERTIES OF LOW-MOLECULAR WEIGHT HEPARIN IN RABBITS

  • 1 January 1982
    • journal article
    • research article
    • Vol. 59  (6) , 1239-1245
Abstract
The hemorrhagic and antithrombotic effects of a low MW (LMW) heparin fraction and standard heparin in rabbits were compared. Similar LMW heparin fractions have antithrombotic effects when tested in animals, but their hemorrhagic effects relative to standard heparin have not been established. Standard porcine mucosal heparin (MW 15,000 daltons) was depolymerized [Dep] by nitrous acid to a low MW fraction (MW 4600 daltons). By using equal USP units, the standard and Dep LMW heparin were compared in vitro, ex vivo and in vivo. In vitro, when diluted in rabbit plasma, the Dep LMW heparin at equivalent anti-Xa activity showed less prolongation of thrombin clotting times or activated partial thromboplastin times. Ex vivo, platelets from rabbits treated with the Dep LMW heparin showed less inhibition of collagen-induced aggregation. The relative hemorrhagic properties of the 2 heparins were compared in vivo in rabbits with a sensitive blood loss assay, and the antithrombotic properties were compared in a thrombin-induced venous stasis model. By using an optimal threshold heparin dose in each test system, it was possible to demonstrate that equal USP units of Dep LMW heparin caused less blood loss but showed greater antithrombotic activity than standard heparin.