The reduced anticoagulant effect of fondaparinux at low antithrombin levels.

Full 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.

Author information

Author/s: Dempfle, Carl-Erik (CE); Eichner, Julia (J); Suvajac, Nenad (N); Ahmad-Nejad, Parviz (P); Neumaier, Michael (M); Borggrefe, Martin (M);

Affiliation: I. Department of Medicine, University Medical Centre Mannheim, Mannheim, Germany. carl-erik.dempfle(-atsign-)umm.de

Journal and publication information

Publication Type: Journal Article

Journal: Anesthesia and analgesia (Anesth Analg), published in United States. (Language: eng)

Reference: 2009-Sep; vol 109 (issue 3) : pp 712-6

Dates: Created 2009/08/19; Completed 2009/09/09;

PMID: 19690236, status: MEDLINE (last retrieval date: 9/9/2009, IMS Date: )

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