TISSUE FACTOR PATHWAY INHIBITOR AND ANTI-FXA KINETIC PROFILES OF A NEW LOW-MOLECULAR-MASS HEPARIN, BEMIPARIN, AT THERAPEUTIC SUBCUTANEOUS DOSES

Low-molecular-mass heparins (LMMHs) exert an anti-FXa effect through a ntithrombin III (ATIII) and tissue factor pathway inhibitor (TFPI) dis placed from endothelium and lipoproteins. This global anti-FXa potency is specific for different compounds. Whether these effects have a sim ilar kinetic and duration is a matter of interest. We compared the kin etic profile of the TFPI effect (total and free) to the anti-FXa amido lytic activity induced by therapeutic subcutaneous doses of a new LMMH , Bemiparin. The overall kinetics of the anti-FXa amidolytic activity and the TFPI effect were different, TFPI achieving a maximal effect ea rlier than the anti-FXa activity and completely disappearing before it . The anti-FXa amidolytic activity of Bemiparin followed a linear dose -response pattern. Neither total nor free TFPI was directly proportion al to the dose. At therapeutic subcutaneous doses, Bemiparin exerted a n anti-FXa effect through TFPI during the first 2 h, through both ATII I and TFPI during the following 8 h (range 2-10 h) and through ATIII d uring the last 8 h (range 10-18 h). (C) 1998 Lippincott-Raven Publishe rs.