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).
Falkon
L
L
Unitat d'Hemostàsia i Trombosi, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain.
Garí
M
M
Barbanoj
M
M
Amiral
J
J
Fontcuberta
J
J
D000328:Adult; D000704:Analysis of Variance; D000925:Anticoagulants / Q000493:pharmacokinetics / Q000627:therapeutic use*; D000990:Antithrombin III / Q000378:metabolism*; D018592:Cross-Over Studies; D004305:Dose-Response Relationship, Drug; D065427:Factor Xa Inhibitors; D006495:Heparin, Low-Molecular-Weight / Q000493:pharmacokinetics / Q000627:therapeutic use*; D006801:Humans; D007279:Injections, Subcutaneous; D008074:Lipoproteins / Q000378:metabolism*; D008297:Male; D012016:Reference Values
D000925:Anticoagulants; D065427:Factor Xa Inhibitors; D006495:Heparin, Low-Molecular-Weight; D008074:Lipoproteins; C051928:lipoprotein-associated coagulation inhibitor; D000990:Antithrombin III