How Should Enoxaparin Be Dosed for VTE Prevention?

Laura S. Lehman, PharmD

Disclosures

February 15, 2011

Question:

Is there any rationale for using therapeutic doses of enoxaparin for patients needing venous thromboembolism prevention?

Response from Laura S. Lehman, PharmD
Pharmacist, Carroll Hospital Center, Westminster, Maryland

US Food and Drug Administration-approved dosing of enoxaparin for prevention of deep venous thrombosis depends on the specific indication, and varies from 40 mg subcutaneously (SC) once daily to 30 mg SC every 12 hours for patients with normal renal function.[1] The American College of Chest Physicians (ACCP) advises clinicians to follow manufacturer recommendations for antithrombotic dosing.[2]

However, the guidelines do have a few "exceptions," such as recommending use of higher-prophylaxis dosing in obese patients.[2] Interpreting what this "higher" dose is may be challenging. Also, one may wonder why warfarin used for venous thromboembolism (VTE) prophylaxis often has the same international normalized ratio of 2-3 as treatment dosing when standard enoxaparin prophylaxis doses are lower than treatment doses.

Previous thrombosis is a risk factor for development of VTE. Patients with a history of VTE were included in early studies of enoxaparin for VTE prophylaxis.[3] Furthermore, studies, such as the MEDical patients with ENOXaparin (MEDENOX) trial, included acutely ill patients with a history of VTE.[4] A post hoc analysis of the MEDENOX trial found a 51% reduction in rate of VTE (absolute risk reduction, 12.2%) in patients with a history of previous VTE receiving enoxaparin 40 mg SC daily compared with placebo.[5] Therefore, nonpregnant, nonobese medical and surgical patients with a history of VTE who are not chronically anticoagulated should receive the same enoxaparin dose for VTE prophylaxis as those without a history of VTE.

In obese patients, weight-based dosing of low-molecular-weight heparins (LMWH) is recommended on the basis of data showing reduced anti-Xa levels with an increase in weight.[6] However, the optimal weight-based dose remains to be established. Suggested prophylactic enoxaparin regimens that are based on small studies in morbidly obese patients include 30% increases in usual LMWH dose, 40 mg SC every 12 hours, and 0.5 mg/kg SC once daily.[6,7,8] Additional consideration can be given to monitoring peak anti-Xa levels (4 hours post dose) with a goal of 0.2-0.4 IU/mL for VTE prophylaxis in obese patients.[6] However, this strategy requires further clinical review before becoming standard of care.

For pregnant patients, the ACCP guidelines for dosing of enoxaparin vary. Depending on VTE history, presence of thrombophilia, and use of a mechanical valve, the enoxaparin dose could be 40 mg SC once daily, 40 mg SC every 12 hours, 75% of treatment dose, or treatment dose of 1 mg/kg SC every 12 hours.[9]

VTE prophylaxis regimens are not 100% effective in any group of patients, and there will be occasional failures of antithrombotic therapy. On the basis of an individualized patient risk and benefit assessment, a clinician may feel compelled to prescribe a more aggressive dose than what is either FDA approved or advocated in national guidelines. This practice is not recommended without clinical evidence of efficacy and safety. It remains to be seen whether individualized LMWH titration according to an optimal level of anti-Xa activity would prove safer and more effective in subgroups of patients. Unfortunately, such a process would reverse the widely touted benefit of a lack of monitoring required with LMWH.

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