fondaparinux and Liver-Diseases

fondaparinux has been researched along with Liver-Diseases* in 1 studies

Other Studies

1 other study(ies) available for fondaparinux and Liver-Diseases

ArticleYear
Functionality of fondaparinux (pentasaccharide) depends on clinical antithrombin levels.
    Blood coagulation & fibrinolysis : an international journal in haemostasis and thrombosis, 2011, Volume: 22, Issue:3

    Fondaparinux (Arixtra) is an antithrombin (AT)-dependent synthetic inhibitor of factor Xa (FXa). We undertook a study to determine the ramifications of varying levels of circulating AT on the pharmacologic activity of fondaparinux. AT-deficient human plasma supplemented with 0.125-2.0 U/ml purified human AT and plasmas from liver disease patients (n = 20; 0.3 U/ml AT) were supplemented with fondaparinux (0.125-12.5 μg/ml) then assayed by an amidolytic anti-FXa assay and the clot-based Heptest. A decrease in fondaparinux activity was observed with AT levels of 0.5 U/ml that became more pronounced with decreasing AT levels. For 0.2-1.5 μg/ml fondaparinux (plasma concentrations achieved with dosages for prophylaxis and treatment of venous thromboembolism) and AT levels of 0.5 U/ml there was 20% loss of activity and with 0.25 U/ml AT there was a 45% loss of activity compared to 1 U/ml AT. Increasing AT levels to over 0.5 U/ml or increasing fondaparinux concentrations for AT levels between 0.5 and 1 U/ml achieved fondaparinux activity comparable to that obtained with 1 U/ml AT. With AT levels above 1.0 U/ml a greater inhibitory activity was achieved. The observed potency of fondaparinux in terms of anti-FXa activity was reduced approximately three-fold in patients with liver disease. These in-vitro findings were confirmed in a rabbit model of stasis thrombosis. With AT levels below 30% of normal induced by anti-AT antibodies, there was a 60% in-vivo reduction in the antithrombotic activity of fondaparinux (ED50 75 vs. 240 μg/kg). In summary, the AT level is a rate-limiting factor for the antithrombotic activity of fondaparinux.

    Topics: Animals; Anticoagulants; Antithrombin Proteins; Factor Xa Inhibitors; Fondaparinux; Humans; Liver Diseases; Polysaccharides; Rabbits; Thrombosis

2011