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*
Anesthesia Analgesia 2009; 109:712-716
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@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.
--
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