Dr. Le is a pharmacy practice resident at Fountain Valley Regional Hospital and Medical Center in Fountain Valley, California. Dr. Pham is assistant professor of pharmacy practice at Western University College of Pharmacy and Health Sciences in Pomona, California.
A major cause of morbidity and mortality in the health system is venous thromboembolism (VTE). VTE includes both deep vein thrombosis (DVT) and pulmonary embolism (PE). Evidence-based practice guidelines have been developed for the prophylaxis of VTE. Currently, unfractionated heparin (UFH), low-molecular-weight heparin (LMWH), and selective factor Xa inhibitor (fondaparinux) are all approved for the prevention of VTE.
The most current guidelines for VTE prophylaxis are based on the 2004 Seventh American College of Chest Physicians (ACCP) Conference on Antithrombotic and Thrombolytic Therapy.1 The guideline for VTE prophylaxis is based on solid principles, and recommendations are made based on risk levels. All recommendations have been considered Grade 1, which indicate a strong benefit-to-risk ratio. Regardless, it is important to emphasize that the final decision regarding the use and nature of prophylaxis lies with the individual clinician.
VTE prophylaxis methods are divided into 2 categories: mechanical methods and pharmacologic methods. Mechanical methods include the use of graduated compression stockings (GCS), intermittent pneumatic compression (IPC) devices, and venous foot pumps which all help increase venous blood outflow and reduce stasis within the leg veins. Mechanical methods have been shown to reduce the risk of VTE in a number of patient groups; however, they have been studied less than anticoagulant-based prophylaxis and are generally less efficacious. The use of mechanical devices should be considered in patients at high risk for bleeding. Mechanical devices can be used alone or in combination with pharmacologic methods. Although concerns have been raised regarding the bleeding complications associated with pharmacologic thromboprophylaxis, abundant data exist to show a desirable risk-to-benefit ratio.
The guidelines recommend that all patients be assessed for their risk of VTE. The selection of prophylaxis depends on the individual's risk factors for VTE and the type of surgery he or she may be undergoing. After identifying a patient's risk factors, it is important to assign risk levels based on the type of surgery (Table). Several key recommendations include the following:
It also is recommended that pharmacologic thromboprophylaxis with LDUH be given 2 to 3 times daily and used in all patients undergoing major gynecologic surgery or major open urologic procedures.
For patients undergoing elective total hip or knee arthroplasty, 1 of the following 3 anticoagulant agents can be used: LMWH, fondaparinux, or adjusted-dose warfarin with international normalized ratio target range from 2.0 to 3.0. For patients undergoing hip fracture surgery, routine use of fondaparinux, LMWH, warfarin, or LDUH can be used and continued for at least 10 days. All trauma patients with at least 1 risk factor for VTE should receive thromboprophylaxis. In acutely ill medical patients who have been admitted to the hospital with heart failure or severe respiratory distress, or who are confined to the bed and have 1 or more additional risk factors, prophylaxis with LDUH or LMWH should be considered.
The required duration or extended use of prophylaxis may need to be continued in some patients after discharge. Further studies are required to address this issue, and individual clinical judgment should be used.
In July 2007, Wein et al performed a meta-analysis that included 36 randomized controlled trials to determine which pharmacologic agents were most effective in preventing VTE in hospitalized medical patients.2
This meta-analysis concluded that the use of LMWH, LDUH, and fondaparinux were associated with a statistically significant reduced risk of DVT and PE and increased risk of total bleeding, compared with no prophylaxis. DVT was prevented more effectively when LDUH was administered 5000 units 3 times daily, compared with 5000 units twice daily. Neither LDUH nor LMWH were shown to have any effects on mortality reduction. When compared directly, it appeared that LMWH was one third more effective than LDUH in preventing DVT. Also, patients taking LMWH exhibited lower risk of injection site hematoma than LDUH. Furthermore, no significant difference was observed between LMWH and LDUH in terms of bleeding and thrombocytopenia. No statistically significant differences were observed between the 2 agents in regard to PE.
Before we can implement any major changes and deviate from current practice, we must weigh the strengths and weaknesses of this meta-analysis. For example, only 10 of the 36 trials reviewed directly compared LMWH with LDUH. Also, the patient population from the 36 trials was not homogeneous. Finally, the type of LMWH used among the trials reviewed was not consistent.
Pharmacy and therapeutic committees within the health system should evaluate the use of LDUH, LMWH, and fondaparinux, as all 3 agents have been recommended for VTE prophylaxis in the ACCP guidelines. Priority should be given to agents that produce the most therapeutic benefit with the least adverse effects and the least cost.
The ACCP guidelines recommend the use of LDUH, LMWH, and fondaparinux in medical patients at risk for VTE. Pharmacists must keep abreast of this information in order to select the best agents for their patients.
Answers: 1. d; 2. d; 3. b
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