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CARDIOVASCULAR ANESTHESIOLOGY

The Reduced Anticoagulant Effect of Fondaparinux at Low Antithrombin Levels

Carl-Erik Dempfle, Prof Dr med^*, Julia Eichner^*, Nenad Suvajac^*, Parviz Ahmad-Nejad, Dr med, Michael Neumaier, Prof Dr med, and Martin Borggrefe, Prof Dr med^*

From the *I. Department of Medicine, and Institute for Clinical Chemistry, University Medical Centre Mannheim, Mannheim, Germany.

Address correspondence and reprint requests to Carl-Erik Dempfle, I. Department of Medicine, University Medical Centre Mannheim, Theodor Kutzer Ufer 1-3, D-68167 Mannheim, Germany. Address e-mail to carl-erik.dempfle{at}umm.de.

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 µg/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.