title: A supersulfated low-molecular-weight heparin (IK-SSH) increases plasma levels of free and total tissue factor pathway inhibitor after intravenous and subcutaneous administration in humans.
abstract: Unfractionated as well as low-molecular-weight heparins (LMWH) are known to cause an increase in blood levels of tissue factor pathway inhibitor (TFPI). To study the effect of a newly developed supersulfated LMWH (IK-SSH, Iketon Farmaceutici) on TFPI concentrations in human plasma, the compound was injected into volunteers at doses of 0.14, 0.33 and 0.66 mg/kg intravenously or 0.33, 0.66 and 1.0 mg/kg subcutaneously. At certain known times blood was drawn and plasma levels of both total and free TFPI were measured using enzyme-linked immunosorbent assay methodology. Baseline plasma concentrations of TFPI were 72.2+/-3.1 ng/ml for total and 10.8+/-0.8 ng/ml for free TFPI. Intravenous or subcutaneous injection of IK-SSH led to a strong and long-lasting rise in TFPI levels which were increased more than 5-fold for total TFPI and more than 30-fold for free TFPI. Maximum TFPI levels were reached 5-10 min after intravenous and 60 min after subcutaneous administration. IK-SSH caused prolongation of ex-vivo clotting times in the APTT and Heptest assay, whereas thrombin time was not affected. Anticoagulant actions of IK-SSH showed a significant correlation to plasma concentrations of TFPI and they are thought to be based at least partially on the release of TFPI from vascular sites.
authors.affiliation: Friedrich Schiller University Jena, Center for Vascular Biology and Medicine Erfurt, Germany. kaiser@zmkh.ef.uni-jena.de
authors.forename: B
authors.initials: B
authors.lastname: Kaiser
authors.forename: E
authors.initials: E
authors.lastname: Glusa
authors.forename: D A
authors.initials: DA
authors.lastname: Hoppensteadt
authors.forename: H K
authors.initials: HK
authors.lastname: Breddin
authors.forename: J
authors.initials: J
authors.lastname: Amiral
authors.forename: J
authors.initials: J
authors.lastname: Fareed
mesh_terms: D000328:Adult; D000925:Anticoagulants / Q000494:pharmacology*; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006495:Heparin, Low-Molecular-Weight / Q000008:administration & dosage / Q000494:pharmacology*; D006801:Humans; D007275:Injections, Intravenous; D007279:Injections, Subcutaneous; D007700:Kinetics; D008074:Lipoproteins / Q000097:blood*; D008297:Male; D013431:Sulfates / Q000008:administration & dosage / Q000494:pharmacology*
chemical_list: D000925:Anticoagulants; D006495:Heparin, Low-Molecular-Weight; D008074:Lipoproteins; D013431:Sulfates; C051928:lipoprotein-associated coagulation inhibitor