Thromboembolism fondaparinux

Fondaparinux, the factor Xa-binding pentasaccharide (Arixtra, MW 1,728 Da), is prepared synthetically, unlike UFH, LMWH and danaparoid, which are obtained from animal sources. Despite only inactivating free factor Xa, clinical trials indicate that fondaparinux is an effective antithrombotic agent, both for venous thromboembolism prophylaxis and treatment, as well as for acute coronary syndrome and ST elevation myocardial infarction [4]. 

Mechanism of action of unfractionated heparin, low-molecular-weight heparin (LMWH), and fondaparinux. (Reproduced from Haines ST, Zeolla M, Witt DM. Venous thromboembolism. In DiPiro JT, Talbert RL, Yee GC, et al, (eds.) Pharmacotherapy ... 

Spinal/Epidural hematomas When neuraxial anesthesia (epidural/spinal anesthesia) or spinal puncture is employed, patients anticoagulated or scheduled to be anticoagulated with low molecular weight heparins (LMWHs), heparinoids, or fondaparinux for prevention of thromboembolic complications are at risk of developing an epidural or spinal hematoma that can result in long-term or permanent paralysis. 

In a double-blind, randomized study of 2309 consecutive patients undergoing elective hip replacement, postoperative subcutaneous fondaparinux 2.5 mg/day was compared with preoperative enoxaparin 40 mg/day (19). By day 11, venous thromboembolism had occurred in 85 (9%) of 919 patients assigned to enoxaparin and in 37 (4%) of 908 patients assigned to fondaparinux, a relative risk reduction of 56% (95% Cl = 33, 73). In a similar comparison of postoperative fondaparinux 2.5 mg/day and enoxaparin 30 mg bd in 2275 consecutive patients undergoing elective hip replacement, by day 11 venous thromboembolism had occurred in 48 (6%) of 787 patients assigned to fondaparinux and in 66 (8%) of 797 patients assigned to enoxaparin, a relative risk reduction of 26% (95% Cl = 11, 53) (20). 

Eriksson Bl, Bauer KA, Lassen MR, Turpie AG Steering Committee of the Pentasaccharide in Hip-Fracture Surgery Study. Fondaparinux compared with enoxaparin for the prevention of venous thromboembolism after hip-fracture surgery. N Engl J Med 2001 345(18) 1298-304. 

Lassen MR, Bauer KA, Eriksson Bl, Turpie AG European Pentasaccharide Elective Surgery Study (EPHESUS) Steering Committee. Postoperative fondaparinux versus preoperative enoxaparin for prevention of venous thromboembolism in elective hip-replacement surgery a randomised double-bhnd comparison. Lancet 2002 359(9319) 1715-20. 

Fondaparinux vs enoxaparin for the prevention of venous thromboembolism in major orthopedic surgery a metaanalysis of 4 randomized double-bhnd studies. Arch Intern Med 2002 162(16) 1833-40. 

Turpie AG, Eriksson Bl, Lassen MR, Bauer KA. A metaanalysis of fondaparinux versus enoxaparin in the prevention of venous thromboembolism after major orthopaedic surgery. J South Orthop Assoc 2002 ll(4) 182-8. 

Warfarin monotherapy is an unacceptable choice for the acute treatment of VTE because it does not produce a rapid anticoagulation effect and is associated with a high incidence of recurrent thromboembolism. However, warfarin is very effective in the longterm management of VTE and should be started concurrently with UFH, LMWH, or fondaparinux therapy. The acute treatment regimen should overlap with warfarin therapy for at least 5 days and until a therapeutic INR has been achieved. The initial dose of warfarin should be 5 to 10 mg (see Fig. 19-8), and it should be adjusted periodically to achieve and maintain an INR between 2.0 and 3.0. 

Eriksson BI, Lassen MR. Duration of prophylaxis against venous thromboembolism with fondaparinux after hip fracture surgery A multi center,... 

Posnett J, Gordois A. Cost-effectiveness of fondaparinux vs enoxaparin as prophylaxis against venous thromboembolism following orthopaedic surgery. Value Health 2002 5 444. 

LMW heparin, enoxaparin, for preventing VTE after major orthopedic surgery (30). The results from a meta-analysis show thiat fondaparinux (10) is associated with an overall risk reduction versus enoxaparin for the prevention of venous thromboembolism. Of aiU the LMW heparins, enoxaparin is widely regarded as the treatment standard for VTE prophylaxis. Fondaparinux (10) is an injectable solution for the prevention of DVT and is the only antithrombotic agent approved in the United States for hip fracture surgery. 

Eikelboom JW, Quinlan DJ, O Doimell M. Major bleeding, mortality, and efficacy of fondaparinux in venous thromboembolism prevention trials. Circulation 2009 120(20) 2006-11. 

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