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 antithrombin III (ATIII) and tissue factor pathway inhibitor (TFPI) displaced from endothelium and lipoproteins. This global anti-FXa potency is specific for different compounds. Whether these effects have a similar kinetic and duration is a matter of interest. We compared the kinetic profile of the TFPI effect (total and free) to the anti-FXa amidolytic 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 earlier 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 proportional to the dose. At therapeutic subcutaneous doses, Bemiparin exerted an anti-FXa effect through TFPI during the first 2 h, through both ATIII and TFPI during the following 8 h (range 2-10 h) and through ATIII during the last 8 h (range 10-18 h).