The reduced anticoagulant effect of fondaparinux at low antithrombin levels.
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.
Dempfle
Carl-Erik
CE
I. Department of Medicine, University Medical Centre Mannheim, Mannheim, Germany. carl-erik.dempfle@umm.de
Eichner
Julia
J
Suvajac
Nenad
N
Ahmad-Nejad
Parviz
P
Neumaier
Michael
M
Borggrefe
Martin
M
D000925:Anticoagulants / Q000494:pharmacology*; D000991:Antithrombins / Q000737:chemistry / Q000378:metabolism*; D001777:Blood Coagulation / Q000187:drug effects; D001780:Blood Coagulation Tests; D004305:Dose-Response Relationship, Drug; D000077425:Fondaparinux; D006493:Heparin / Q000737:chemistry; D006801:Humans; D011134:Polysaccharides / Q000494:pharmacology*; D012044:Regression Analysis; D016896:Treatment Outcome
D000925:Anticoagulants; D000991:Antithrombins; D011134:Polysaccharides; D006493:Heparin; D000077425:Fondaparinux