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Heparin pentasaccharide.

Alexander S Gallus1, Douglas W Coghlan

  • 1Department of Haematology, Flinders Medical Centre, Belford Park, SA 5042, Adelaide, Australia. alexander.gallus@flinders.edu.au

Current Opinion in Hematology
|August 13, 2002
PubMed
Summary

Fondaparinux, a synthetic pentasaccharide, significantly reduced deep vein thrombosis after major joint surgery compared to low molecular weight heparin. Optimal timing of the first dose may mitigate increased bleeding risk.

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Area of Science:

  • Pharmacology
  • Thrombosis Research
  • Clinical Trials

Background:

  • Fondaparinux is a synthetic heparin analogue targeting Factor Xa.
  • It offers predictable pharmacokinetics and does not require laboratory monitoring.
  • It avoids cross-reactivity with antibodies causing heparin-induced thrombocytopenia.

Purpose of the Study:

  • To evaluate fondaparinux for venous thromboembolism (VTE) prevention post-major joint surgery.
  • To compare the efficacy and safety of fondaparinux with low molecular weight heparin (LMWH).

Main Methods:

  • Four large, randomized, placebo-controlled, double-blind phase III trials.
  • Fondaparinux administered subcutaneously post-surgery versus LMWH (pre- or post-surgery).
  • Efficacy endpoints: subclinical/clinical DVT, symptomatic VTE. Safety endpoint: major bleeding.

Main Results:

  • Fondaparinux reduced VTE rates by 26-63% across different joint surgeries compared to LMWH.
  • Statistically significant reductions in proximal deep vein thrombosis (DVT) were observed.
  • A trend towards increased major bleeding with fondaparinux was noted, potentially linked to early administration.

Conclusions:

  • Fondaparinux demonstrates superior efficacy in preventing VTE after major joint surgery compared to LMWH.
  • The lowest DVT rates post-surgery were achieved with fondaparinux.
  • Adjusting the first dose timing to 6-8 hours post-surgery may optimize the safety profile without compromising efficacy.

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