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Deep vein thrombosis (DVT) occurs when the flow of blood is restricted and a clot forms. A clot most commonly forms in the legs following surgery, where it can then mobilize into the lungs and become fatal. Complications from DVT contribute to more deaths each year than AIDS and breast cancer combined.1 DVT has an average occurrence of 24% to 27% following hip fracture surgery, 31% to 47% following knee replacement surgery, and 16% to 30% following hip replacement surgery.2 Postsurgery complications eventually can lead to pulmonary embolism, which has a 10% mortality rate.2 Arixtra, marketed by GlaxoSmithKline, is indicated for the prophylaxis of DVT in hip fracture surgery, knee replacement surgery, and hip replacement surgery.3
Arixtra is a pentasaccharide antithrombotic agent and the only synthetic selective factor Xa inhibitor. Selective binding to antithrombin III neutralizes Xa, which then interrupts the blood coagulation cascade. This disruption inhibits thrombin formation and thrombus development. Arixtra is not a heparin and does not directly inhibit thrombin. At the recommended dose, it does not affect fibrinolytic activity or bleeding time.3
In a double-blind, randomized study, researchers assigned 2309 patients who were undergoing elective hip replacement surgery to once-daily, subcutaneous injections of 2.5 mg fondaparinux, starting postoperatively, or 40 mg enoxaparin, starting preoperatively. The primary efficacy outcome was venous thromboembolism (VTE) up to day 11, defined as DVT detected by mandatory bilateral venography. By day 11, VTEs were recorded in 4% of patients assigned to fondaparinux and in 9% assigned to enoxaparin (difference: -5.2%, P<.0001). The relative risk reduction was 55.9% (95% confidence interval [CI]: 33.1-72.8).4
In another double-blind study, 1049 patients undergoing elective major knee surgery were randomly assigned to receive postoperative subcutaneous doses of either 2.5 mg of fondaparinux once daily or 30 mg of enoxaparin twice daily. The primary efficacy outcome was VTE up to postoperative day 11, defined as DVT detected by mandatory bilateral venography. The fondaparinux group showed a significantly lower incidence of VTE by day 11 (12.5%) than the enoxaparin group (27.8%; 95% CI: 36.2-70.2). Investigators concluded that, in patients undergoing elective major knee surgery, postoperative treatment with once-daily fondaparinux significantly prevented DVT more effectively than enoxaparin twice daily.5
There has been no reported incidence of immune-mediated heparin-induced thrombocytopenia associated with Arixtra. If platelet count falls below 100,000/mm, however, Arixtra should be discontinued.3 After discontinuation, its anticoagulant effects may persist for 2 to 4 days in patients with normal renal function and longer in patients with renal impairment. Patients should be monitored frequently for signs and symptoms of neurologic impairment. Arixtra is contraindicated in patients with severe renal impairment; in patients with body weight <50 kg undergoing hip fracture, hip replacement, or knee replacement surgery; and in patients with active major bleeding or bacterial endocarditis.3
Arixtra should be administered 6 to 8 hours following surgery, because doses given within 6 hours post-surgery have been associated with an increased risk of bleeding.3 Treatment should continue for at least 5 days or until a therapeutic oral anticoagulant effect is established (international normalized ratio 2.0-3.0).
Drs. Faria and Soo are both senior research pharmacists with the Investigational Drug Service at Brigham and Women's Hospital, Boston, Mass. Dr. Faria also is a senior human research specialist with Partners HealthCare System. Ms. Kohl is a sixth-year pharmacy student from West Palm Beach Atlantic University on clinical rotation in the Investigational Drug Service at Brigham and Women's Hospital.
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