The reduced anticoagulant effect of fondaparinux at low antithrombin levels

Anesth Analg. 2009 Sep;109(3):712-6. doi: 10.1213/ane.0b013e3181ae94b0.

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.

MeSH terms

  • Anticoagulants / pharmacology*
  • Antithrombins / chemistry
  • Antithrombins / metabolism*
  • Blood Coagulation / drug effects
  • Blood Coagulation Tests
  • Dose-Response Relationship, Drug
  • Fondaparinux
  • Heparin / chemistry
  • Humans
  • Polysaccharides / pharmacology*
  • Regression Analysis
  • Treatment Outcome

Substances

  • Anticoagulants
  • Antithrombins
  • Polysaccharides
  • Heparin
  • Fondaparinux