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Published on: October 12, 2012
The reduced anticoagulant effect of fondaparinux at low antithrombin levels
Carl-Erik Dempfle1, Julia Eichner, Nenad Suvajac
1I. Department of Medicine, University Medical Centre Mannheim, Mannheim, Germany. carl-erik.dempfle@umm.de
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.
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