title: The reduced anticoagulant effect of fondaparinux at low antithrombin levels.
abstract: BACKGROUND
  Low antithrombin levels may compromise the anticoagulant effect of heparin and heparin-related compounds, such as fondaparinux.
  
  
  METHODS
  We compared the anticoagulant effect of 10 concentrations of fondaparinux added to plasma samples with normal range (n = 25, antithrombin 95.4% +/- 9.2%) and low antithrombin (n = 22, antithrombin 45.5% +/- 13.2%) levels, using the Heptest coagulation assay.
  
  
  RESULTS
  Heptest clotting time was shorter at any given fondaparinux concentration in the antithrombin-deficient samples, indicating less anticoagulant effect than in the group with normal antithrombin levels. At a high fondaparinux concentration, a saturation effect is observed with no further increase in Heptest clotting time. Addition of antithrombin concentrates results in a shift of the dose-response curve. When antithrombin concentrate was added, Heptest clotting time increased up to a fondaparinux concentration of 10 microg/mL.
  
  
  CONCLUSIONS
  In the conventional prophylactic and therapeutic dose range, not only treatment with antithrombin concentrates but also an increase in fondaparinux dose normalizes the anticoagulant effect. A saturation effect is observed at high fondaparinux concentrations. Higher levels of antithrombin lead to an exaggerated effect of fondaparinux on Heptest.
authors.affiliation: I. Department of Medicine, University Medical Centre Mannheim, Mannheim, Germany. carl-erik.dempfle@umm.de
authors.forename: Carl-Erik
authors.initials: CE
authors.lastname: Dempfle
authors.forename: Julia
authors.initials: J
authors.lastname: Eichner
authors.forename: Nenad
authors.initials: N
authors.lastname: Suvajac
authors.forename: Parviz
authors.initials: P
authors.lastname: Ahmad-Nejad
authors.forename: Michael
authors.initials: M
authors.lastname: Neumaier
authors.forename: Martin
authors.initials: M
authors.lastname: Borggrefe
mesh_terms: D000925:Anticoagulants / Q000494:pharmacology*; D000991:Antithrombins / Q000737:chemistry / Q000378:metabolism*; D001777:Blood Coagulation / Q000187:drug effects; D001780:Blood Coagulation Tests; D004305:Dose-Response Relationship, Drug; D000077425:Fondaparinux; D006493:Heparin / Q000737:chemistry; D006801:Humans; D011134:Polysaccharides / Q000494:pharmacology*; D012044:Regression Analysis; D016896:Treatment Outcome
chemical_list: D000925:Anticoagulants; D000991:Antithrombins; D011134:Polysaccharides; D006493:Heparin; D000077425:Fondaparinux