Optimization of Enoxaparin Dosing in Obese Patients
Obesity is a risk factor for venous thromboembolism; however, there is uncertainty regarding the optimal dose of enoxaparin for treating acute episodes in the obese population. Two observational studies published last year focused on the efficacy and safety of enoxaparin depending on the dose. The standard dose of 1 mg/kg may be too high for some patients, and fixed dosing without monitoring Xa levels may not be adequate.
Obesity and Its Impact on Thromboembolism Treatment
Enoxaparin is a low molecular weight heparin (LMWH) used for the prevention and treatment of venous thromboembolism (VTE). Patients with a high body mass index (BMI) are at a higher risk of overdosing, as pharmacokinetics in this population is not well defined. The distribution volume of enoxaparin is similar to blood plasma volume, and the drug does not distribute into adipose tissue.
The standard recommended dosing of enoxaparin for VTE treatment is 1 mg/kg twice daily. The Czech Angiology Society CLS JEP recommends monitoring clinical LMWH levels using anti-Xa levels in extremely obese patients, which should usually be between 0.6-1.2 IU/ml when applied twice daily. Monitoring is done 3-4 hours post LMWH administration.
Opinions among international professional societies on optimal dosing for obese patients vary. Clinical study data suggest that standard dosing may lead to supratherapeutic levels in obese patients.
Safety of Standard Dosing in Obese Patients
A retrospective analysis of data from 102 patients with BMI ≥ 40 kg/m2, treated at Johns Hopkins Hospital in Baltimore, USA, evaluated the incidence of bleeding during enoxaparin treatment. The average initial dose of enoxaparin was 1.0 ± 0.1 mg/kg, and the average final dose was 0.9 ± 0.2 mg/kg. The incidence of bleeding was 4.9%, with the average enoxaparin dose among bleeding patients being 0.7 ± 0.1 mg/kg. Patients with bleeding had a higher BMI (average 51.6 vs. 48.0 kg/m2) compared to those without bleeding. Entry anti-Xa values were available for 71 patients, with 59.2% evaluated as supratherapeutic.
The authors conclude that the initial enoxaparin dose of 1 mg/kg may be too high for obese patients. Data from this study do not allow for conclusions regarding the optimal dose.
BMI-Stratified Dosing Regime
A retrospective observational study by Australian doctors from the Royal Perth Hospital compared data from 47 obese patients treated for VTE (median BMI 36.3 kg/m2) using a BMI-stratified dosing protocol and 46 obese patients (median weight 160 kg) receiving thromboprophylaxis, with data from 20 non-obese controls. Anti-Xa levels were used to evaluate the efficacy of enoxaparin.
The median target anti-Xa level of 0.79 IU/ml was achieved in 58% of obese patients treated for VTE, with dose reduction needed in 25% of patients, dosage increase in 16%. Mild bleeding occurred in 10% of patients, severe bleeding in 2%, and venous thromboembolism in 2%.
Thromboprophylaxis was administered to obese patients in a dose of 40 mg twice daily, achieving target anti-Xa levels of 0.22 IU/ml in 59% of patients. Mild bleeding was observed in 2%, with no severe bleeding or thromboembolic events. Enoxaparin was administered to non-obese control patients at 40 mg twice daily, with no thromboembolic events and mild bleeding observed in 5% of patients.
Conclusion
A BMI-stratified enoxaparin dosing regimen for VTE treatment may be a safe and effective approach for obese patients, with anti-Xa level monitoring being crucial for assessing efficacy and preventing overdosing. Thromboprophylaxis with 40 mg enoxaparin twice daily was effective in preventing thromboembolic events in obese patients without excessive bleeding.
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Sources:
1. Berger O., Sebaaly J., Crawford R. et al. Evaluation of a treatment-dose enoxaparin protocol for patients with obesity. J Pharm Pract 2021 Jun 10: 8971900211022300, doi: 10.1177/08971900211022300.
2. Martin A. M., Polistena P., Mahmud A. et al. Optimal enoxaparin dosing strategies for venous thromboembolism prophylaxis and treatment of high body weight patients. Thromb Res 2021; 207: 116−122, doi: 10.1016/j.thromres.2021.09.002.
3. Hirmerová J., Karetová D., Malý R. et al. Acute venous thrombosis. Guidelines. Czech Angiology Society CLS JEP, 2020. Available at: www.angiology.cz/Angiology/media/system/guidelines/DP_CAS_akutni_zilni_tromboza_2020.pdf
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