title: Dose-dependent release of endogenous tissue factor pathway inhibitor by different low molecular weight heparins.
abstract: Tissue factor pathway inhibitor (TFPI) is released to circulating blood after intravenous and subcutaneous injections of heparins, and may thus contribute to the antithrombotic effect of heparins. A previous study suggested different abilities of various low molecular weight heparins (LMWH) to release endogenous TFPI, but the dose-response relationship was not determined. In the present study, the dose-response relationship for escalating doses of two LMWHs, dalteparin and enoxaparin, on the release of endogenous TFPI was investigated. Six healthy male participants were given 50, 100 and 200 U/kg dalteparin and 0.5, 1.0 and 2.0 mg/kg enoxaparin as a single subcutaneous injection. The study was a randomized, cross-over design with a 1-week wash-out period between each injection. Peak free TFPI antigen and TFPI activity were detected after only 1 h, whereas anti-activated factor X (anti-FXa) and anti-activated factor II (anti-FIIa) activities were detected after 2-6 h. Putative therapeutic equivalent doses of dalteparin and enoxaparin gave similar release of endogenous TFPI, but dissimilar effects on anti-FXa and anti-FIIa activities.
authors.affiliation: Department of Haematology, Ullevål University Hospital, Oslo, Norway. bjorn.bendz@ioks.uio.no
authors.forename: B
authors.initials: B
authors.lastname: Bendz
authors.forename: T O
authors.initials: TO
authors.lastname: Andersen
authors.forename: P M
authors.initials: PM
authors.lastname: Sandset
mesh_terms: D000328:Adult; D000925:Anticoagulants / Q000008:administration & dosage*; D004305:Dose-Response Relationship, Drug; D015951:Factor Xa / Q000378:metabolism; D006495:Heparin, Low-Molecular-Weight / Q000008:administration & dosage* / Q000097:blood / Q000493:pharmacokinetics; D006801:Humans; D008074:Lipoproteins / Q000097:blood / Q000378:metabolism*; D008297:Male; D011516:Prothrombin / Q000378:metabolism; D013997:Time Factors
chemical_list: D000925:Anticoagulants; D006495:Heparin, Low-Molecular-Weight; D008074:Lipoproteins; C051928:lipoprotein-associated coagulation inhibitor; D011516:Prothrombin; C025337:Factor IIa; D015951:Factor Xa