Year 2010 Vol. 18 No 6




Fondaparinux is the first of a class of selective antithrombin-dependent factor Xa inhibitors, it is a synthetic analogue of the critical pentasaccharide sequence required for binding heparin molecules to Anthitrobin. It does not interact with plasma proteins other than antithrombin, leading to a predictable pharmacokinetics, which renders monitoring and dose adjustment unnecessary. Given subcutaneously, fondaparinux demonstrates 100% bioavailability with a half-life of 17 hours permitting once-daily injection. Fondaparinux is more effective than low molecular weight heparin (LMWH) for prevention of venous thromboembolism (VTE) following major orthopedic surgery and at least as effective as for LMWH following major abdominal surgery. Several thousands of patients have been studied and the substance is safe, although a slightly higher frequency of bleedings is found than in patients on LMWH. Other side-effects are rare. Fondaparinux is cost saving and sometimes cost neutral when compared with enoxaparin. It was recommended with a Grade1A rating for VTE prophylaxis in major orthopedic and abdominal surgery. Moreover Fondaparinux was the only anticoagulant recommended with a Grade 1A rating for hip-fracture surgery.

Keywords: fondaparinux, venous thrombosis, venous thromboembolism, surgery, orthopedic surgery, major abdominal surgery, bleeding complications
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  1. Bick, R. L. Thromboprophylaxis and thrombosis in medical, surgical, trauma, and obstetric/gynecologic patients / R. L. Bick, S. Haas // Hematol. Oncol. Clin. North Am. 2003. Vol. 17. P. 217-258.
  2. Bhattacharyya, T. Rate of and risk factors for acute inpatient mortality after orthopaedic surgery / T. Bhattacharyya, R. Iorio, W. L. Healy // J. Bone Joint Surg. Am. 2002. Vol. 84. P. 562-572.
  3. Prevention of venous thromboembolism: The Eight ed ACCP Conference on Antithrombotic and Thrombolytic Therapy / W. H. Geerts [et al.] // Chest 2008. Vol. 133. P. 387-453.
  4. Meissner, M. H. Venous thromboembolism in trauma: a local manifestation of systemic hypercoagulability? / M. H. Meissner, W. L. Chandler, J. S. J. Elliott // Trauma. 2003. Vol. 54. P. 224-231.
  5. Seagroatt, V. Elective total hip replacement: incidence, emergency readmission rate, and postoperative mortality / V. Seagroatt, H. S. Tan, M. Goldacre // BMJ. 1991. Vol. 303. P. 1431-1435.
  6. Unfractionated Heparin, Low Molecular Weight Heparins, and Pentasaccharide: Basic Mechanism of Actions, Pharmacology, and Clinical Use / R. L. Bick [et al.] // Hematol. Oncol. Clin. N. Am. 2005. Vol. 19. P. 1-51.
  7. Guidelines on the use and monitoring of heparin / T. Baglin [et al.] // BJH. 2006. Vol. 133. P. 19-34.
  8. Treatment and Prevention of Heparin-Induced Thrombocytopenia: Evidence-Based Clinical Practice Guidelines American College of Chest Physicians (8th Edition) / T. E. Warkentin [et al.] // Chest. 2008. Vol. 133. P. 340-380.
  9. Dinwoodey, D. L. Heparins, Low-Molecular-Weight Heparins, and Pentasaccharides / D. L. Dinwoodey // Ansell. Clin. Geriatr. Med. 2006. Vol. 22. P. 1-15.
  10. Structure-activity relationship in heparin: a synthetic pentasaccharide with high affinity for antithrombin III and eliciting high antifactor Xa activity / J. Choay [et al.] // Biochem. Biophys. Res. Commun. 1983. Vol. 116. P. 492-499.
  11. Fondaparinux, a synthetic pentasaccharide: the first in a new class of antithrombotic agents - the selective factor Xa inhibitors / K. A. Bauer [et al.] // Cardiovasc. Drug Rev. 2002. Vol. 20. P. 37-52.
  12. Heparin, low-molecular-weight heparins, and heparin pentasaccharide: basic and clinical differentiation / D. Hoppensteadt [et al.] // Hematol. Oncol. Clin. North Am. 2003. Vol. 17. P. 313-341.
  13. The pharmacokinetics of fondaparinux sodium in healthy volunteers / F. Donat [et al.] // Clin. Pharmacokinet. 2002. Vol. 41. Suppl. 2. P. 1-9.
  14. Bauer, K. A. New pentasaccharides for prophylaxis of deep vein thrombosis: pharmacology / K. A. Bauer // Chest. 2003. Vol. 124. P. 364S370S.
  15. Samama, M. M. Evaluation of the pharmacological properties and clinical results of the synthetic pentasaccharide (fondaparinux) / M. M. Samama, G. T. Gerotziafas // Thromb. Res. 2003. Vol. 109.
  16. P. 1-11.
  17. Pharmacokinetic and clinical data supporting the use of fondaparinux 1.5 mg once daily in the prevention of venous thromboembolism in renally impaired patients / A. G. Turpie [et al.] // Blood Coagulation & Fibrinolysis. 2009. Vol. 20, N 2. P. 114-121.
  18. In vitro comparison of the effect of heparin, enoxaparin and fondaparinux on tests of coagulation / L. A. Linkins [et al.] // Thromb. Res. 2002. Vol. 107. P. 241-244.
  19. Assessment of three chromogenic and one clotting assays for the measurement of synthetic pentasaccharide fondaparinux (Arixtra) anti-Xa activity / F. Depasse [et al.] // J. Thromb. Haemost. 2004. Vol. 2. P. 346-348.
  20. The role of tissue factor pathway inhibitor in the mediation of the antithrombotic actions of heparin and low-molecular-weight heparin / D. A. Hoppensteadt [et al.] // Blood Coag Fibrinolysis. 1995. P. S57-S64.
  21. Greaves, M. Limitations of the Laboratory Monitoring of Heparin Therapy / M. Greaves // Thromb Haemost. 2002. Vol. 87. P. 163-164.
  22. Turpie, A. G. A synthetic pentasaccharide for the prevention of deep-vein thrombosis after total hip replacement / A. G. Turpie, A. S. Gallus, J. A. Hoek. // N. Engl. J. Med. 2001. Vol. 344. P. 619-625.
  23. Postoperative fondaparinux versus preoperative enoxaparin for prevention of venous thromboembolism in elective hip-replacement surgery: a randomized double-blind comparison / M. R. Lassen [et al.] // Lancet 2002. Vol. 359. P. 1715-1720.
  24. Postoperative fondaparinux versus postoperative enoxaparin for prevention of venous thromboembolism after elective hip-replacement surgery: a randomised double-blind trial / A. G. Turpie [et al.] // Lancet. 2002. Vol. 359. P. 1721-1726.
  25. Fondaparinux compared with enoxaparin for the prevention of venous thromboembolism after hip-fracture surgery / B. I. Eriksson [et al.] // N. Engl. J. Med. 2001. Vol. 345. P. 1298-1304.
  26. Fondaparinux compared with enoxaparin for the prevention of venous thromboembolism after elective major knee surgery / K. A. Bauer [et al.] / N. Engl. J. Med. 2001. Vol. 345. P. 1305-1310.
  27. Fondaparinux vs enoxaparin for the prevention of venous thromboembolism in major orthopedic surgery: a meta-analysis of 4 randomized double- blind studies / A. G. Turpie [et al.] // Arch. Intern. Med. 2002. Vol. 162. P. 1833-1840.
  28. Superiority of fondaparinux over enoxaparin in preventing venous thromboembolism in major orthopedic surgery using different efficacy end points / A. G. Turpie, [et al.] // Chest. 2004. Vol. 126. P. 501-508.
  29. New pentasaccharides for the prophylaxis of venous thromboembolism: clinical studies / A. G. Turpie [et al.] // Chest. 2003. Vol. 124. P. 371S-378S.
  30. FLEXTRA: Early vs delayed initiation of postoperative fondaparinux prophylaxis after joint replacement: A clinical outcome study / B. Davidsson [et al.] // Congress ISTH. 2005. Abstr.
  31. Venous thromboembolism after orthopedic surgery: implications of the choice for prophylaxis / A. F. Shorr [et al.] // Thromb. Res. 2007. Vol. 121, N 1. P. 17-24.
  32. Eriksson, B. I. Pentasaccharide in hip-fracture surgery plus investigators. Duration of prophylaxis against venous thromboembolism with fondaparinux after hip fracture surgery: a multicenter, randomized, placebo-controlled, double-blind study / B. I. Eriksson, M. R. Lassen // Arch. Intern. Med. 2003. Vol. 163. P. 1337-1342.
  33. The safety and efficacy of extended thromboprophylaxis with fondaparinux after major orthopedic surgery of the lower limb with or without a neuraxial or deep peripheral nerve catheter: the EXPERT Study / F. J. Singelyn [et al.] // Anesth. Analg. 2007. Vol. 105, N 6. P. 1540-1547.
  34. Randomized clinical trial of postoperative fondaparinux versus perioperative dalteparin for prevention of venous thromboembolism in high-risk abdominal surgery / G. Agnelli [et al.] // Br. J. Surg. 2005. Vol. 92. P. 1212-1220.
  35. Fondaparinux combined with intermittent pneumatic compression vs. intermittent pneumatic compression alone for prevention of venous thromboembolism after abdominal surgery: a randomized, double-blind comparison / A. G. Turpie [et al.] // J. Thromb. Haemost. 2007. Vol. 5, N 9. P. 1854-1861.
  36. Economic and clinical evaluation of fondaparinux vs. enoxaparin for thromboprophylaxis following general surgery / R. Farias-Eisner [et al.] // Curr. Med. Res. Opin. 2009. Vol. 25, N 5. P. 1081-1087.
  37. Nijkeuter, M. Pentasaccharides in the prophylaxis and treatment of venous thromboembolism: a systematic review / M. Nijkeuter, M. V. Huisman // Curr. Opin. Pulm. Med. 2004. Vol. 10. P. 338-344.
  38. Hirsh, J. New anticoagulants / J. Hirsh, M. ODonnell, J. I. Weitz // Blood. 2005. Vol. 105. P. 453-463.
  39. Treatment of postoperative bleeding after fondaparinux with rFVIIa and tranexamic acid / F. Huvers [et al.] // Neth. J. Med. 2005. Vol. 63. P. 184-186.
  40. Ability of recombinant factor VIIa to reverse the anticoagulant effect of the pentasaccharide fondaparinux in healthy volunteers / N. R. Bijsterveld [et al.] // Circulation. 2002. Vol. 106. P. 25502554.
  41. Recombinant factor VIIa partially reverses the inhibitory effect of fondaparinux on thrombin generation after tissue factor activation in platelet rich plasma and whole blood / G. T. Gerotziafas [et al.] // Thromb. Haemost. 2004. Vol. 91. P. 531-537.
  42. Cost and occurrence of thrombocytopenia in patients receiving venous thromboembolism prophylaxis following major orthopaedic surgeries / L. E. Happe [et al.] // J. Thromb. Thrombolysis. 2008. Vol. 26, N 2. P. 125-131.
  43. Thromboembolic Prophylaxis with Fondaparinux in Major Orthopaedic Surgery: Outcomes and Costs / T. D. Szucs [et al.] // Heart Drug. 2005. Vol. 5. P. 121-130.
  44. Reynolds, N. A. Fondaparinux sodium: a review of its use in the prevention of venous thromboembolism following major orthopaedic surgery / N. A. Reynolds, C. M. Perry, L. J. Scott // Drugs. 2004. Vol. 64. P. 1575-1596.
  45. Lobo, B. L. Pharmacoeconomic considerations / B. L. Lobo // Am. J. Health Syst. Pharm. 2003. Vol. 60. Suppl. 7. P. S11-S14.
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