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A systematic review of therapeutic enoxaparin dosing in obesity

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Abstract

Enoxaparin is a hydrophilic drug with obesity having little effect on its apparent volume of distribution, therefore patients with obesity receiving standard 1 mg/kg dosing may be at a higher risk of supratherapeutic dosing. Conversely, dose reducing patients with obesity could place already at risk patients at higher risk of a thrombotic event. Data and recommendations are variable for the most appropriate weight-based dose of therapeutic enoxaparin in obese patients, particularly those a weight > 100 kg or a body mass index (BMI) ≥ 40 kg/m2. The purpose of this systematic review was to globally evaluate these data to surmise optimal dosing recommendations for patients with obesity. A systematic review of English language studies was conducted and identified articles via Pubmed, EMBASE, and the Cochrane Central Register of Controlled Trials (CENTRAL) searches. Studies were included if they reported therapeutic enoxaparin use in adult patients with a BMI ≥ 40 kg/m2 or body weight > 100 kg and the percentage of patients achieving a therapeutic anti-Xa based on a weight-based dose or the weight-based dose required to produce a therapeutic anti-Xa level. Therapeutic attainment of anti-Xa levels were assessed across enoxaparin weight-based dosing categories including a very low dose group: < 0.75 mg/kg, low dose group: 0.75–0.85 mg/kg, and standard dose group: ≥ 0.95 mg/kg. Rates of bleeding and thrombosis were also evaluated. A total of eight studies were included. For anti-Xa level assessment, 682 patients were included. A total of 62% of anti-Xa levels were therapeutic in the very low dose group, 66% in the low dose group, and 42% in the standard dose group. Overall rates of total bleeding and thrombosis were assessed in 798 patients. A total of 29 bleedings (3.6%) occurred, and 27 reported a relationship to dose. Most bleedings, 85.2% (n = 23/27), occurred with doses in the standard dose group (≥ 0.95 mg/kg). Thrombosis occurred in 5 patients (0.6%). Utilization of a reduced weight-based dosing strategy for therapeutic enoxaparin in obese patients may increase the percentage of patients with a therapeutic anti-Xa level.

Key points

1. Current evidence for therapeutic enoxaparin use in obese patients mainly consists of small, retrospective data, but inappropriate dosing may lead to bleeding or thrombotic events.

2. This review identified eight studies that assessed therapeutic enoxaparin dosing in patients with a BMI ≥ 40 kg/m2 or > 100 kg and determined that patients with a reduced dosing regimen (0.75–0.85 mg/kg) achieved goal anti-Xa levels 66% of the time compared to 43% of the time with full weight-based dosing (≥ 0.95 mg/kg).

3. Rates of bleeding occurred in 3.6% of patients, most of which (> 85%) were in the full weight-based dosing group.

4. Use of a reduced weight-based dose of enoxaparin (0.75–0.85 mg/kg) may result in more obese patients with a BMI ≥ 40 kg/m2 or body weight > 100 kg achieving goal anti-Xa levels than full weight-based dosing.

5. Prospective randomized-controlled trials are required to verify clinical outcomes in this population.

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Authors and Affiliations

  1. University at Buffalo School of Pharmacy and Pharmaceutical Sciences, 273 Pharmacy Building, Buffalo, NY, 14214, USA

    Maya R. Chilbert, Kimberly Zammit & Ashley E. Woodruff

  2. Buffalo General Medical Center, 100 High Street, Buffalo, NY, 14203, USA

    Maya R. Chilbert & Ashley E. Woodruff

  3. The Mount Sinai Hospital, 1 Gustave L. Levy Place, New York, NY, 10029, USA

    Kimberly Zammit, Sara Radparvar & Ashley Schuler

  4. Mount Sinai Brooklyn, 3201 Kings Hwy, Brooklyn, NY, 1123, USA

    Uzma Ahmed

  5. Mount Sinai Beth Israel, 281 1st Avenue, New York, NY, 10003, USA

    Amanda Devlin

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Chilbert, M.R., Zammit, K., Ahmed, U. et al. A systematic review of therapeutic enoxaparin dosing in obesity. J Thromb Thrombolysis 57, 587–597 (2024). https://doi.org/10.1007/s11239-024-02951-w

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