DIFFERENTIAL-EFFECTS OF LOW-MOLECULAR-WEIGHT HEPARIN AND UNFRACTIONATED HEPARIN ON CIRCULATING LEVELS OF ANTITHROMBIN AND TISSUE FACTOR PATHWAY INHIBITOR (TFPI) - A POSSIBLE MECHANISM FOR DIFFERENCE IN THERAPEUTIC EFFICACY

There is growing evidence on the superior efficacy and safety of low m olecular weight heparins (LMWHs) over unfractionated heparin (UFH) for the treatment of both venous and arterial thromboembolism. Heparin ex erts its function by potentiating antithrombin and by mobilizing tissu e factor pathway inhibitor (TFPI) into the circulation. The present st udy was conducted to compare the effect of subcutaneous LMWH and infus ion of UFH on these two anticoagulants in plasma. Eighteen healthy mal e volunteers were randomly allocated to therapy with continuous intrav enous (iv) UFH (n=6) (initial infusion rate 450 IU/kg/day) or low mole cular weight heparin (LMWH) (enoxaparin, 1.5 mg/kg/day) subcutaneously (sc) once daily for 72 hours. Free TFPI antigen, measured by a solid- phase two-site enzyme immunoassay, and antithrombin and protein C acti vities, measured by chromogenic assays, were assessed in plasma sample s before, during, and after anticoagulant treatment. Infusion of UFH, but not subcutaneous LMWH, was found to attenuate the antithrombotic d efense by a selective decrease of both circulating antithrombin (-21+/ -7%, p<0.0001) and of free and endothelial-bound TFPI. The changes in antithrombin and TFPI by LMWH and UFH were statistically different bet ween groups (p<0.001). The differential effect of UFH and LMWH on anti thrombin and TFPI may explain the superior efficacy of subcutaneous LM WH compared with conventional intravenous UFH for treatment of both ar terial and venous thrombosis. (C) 1998 Elsevier Science Ltd.