Fondaparinux sodium lacks immunomodulatory effects of heparin

Venous thromboembolism (VTE) remains a frequent complication in orthopedic and trauma patients, despite the use of prophylactic antithrombotic drugs like standard or low molecular weight heparin. A new synthetic pentasaccharide with specific anti-Xa activity (fondaparinux sodium) has been shown to reduce the overall risk of VTE in major orthopedic surgery by 50% without increasing the risk of clinically relevant bleeding, when compared with enoxaparin. Beyond their traditional role as anticoagulants, heparin and low molecular weight heparin possess potent immunomodulatory effects. For example, heparin and enoxaparin enhance endotoxin (lipopolysaccharide)-induced cytokine production in isolated human monocytes and in whole blood. In this study, we investigated the immunomodulatory effects of heparin and fondaparinux sodium.

Treatment of whole blood from 5 healthy volunteers ex vivo with heparin, fondaparinux sodium, and LPS (10 ng/mL, 4 hours). Determination of plasma interleukin (IL)-8 levels, thrombin clotting times, and anti-Xa activity with enzyme-linked immunosorbent assay and the AMAX CS190 device, respectively. Statistical analysis by analysis of variance and Fisher's probable least-squares difference posthoc test.

Heparin concentrations > or =20 IU/mL significantly increased LPS-induced IL-8 production. Fondaparinux sodium, however, did not increase the LPS response. Heparin and fondaparinux sodium exhibited the expected anticoagulatory activities: heparin increased both thrombin clotting time and anti-Xa activity, fondaparinux sodium increased anti-Xa activity only.

Fondaparinux sodium is not an immunomodulator like heparin, suggesting that this novel compound may lack adverse effects in endotoxemic patients. Further studies will establish whether fondaparinux sodium can safely be administered to patients with endotoxemia or sepsis.