Abstract
Background: In clinical trials assessing venous thromboemobolism (VTE) management, patients with obesity are under-represented or specifically excluded. The International Society on Thrombosis and Haemostasis advises against direct-acting oral anticoagulants in patients >120kg(1). Therefore, low-molecular weight heparin and warfarin remain the standard of care in this population.
Objective: To assess weight-based enoxaparin dosing in VTE, with no capping of prescribed doses, comparing patients weighing >100kg with those weighing <100kg. The primary outcome was anti-Xa activity levels, as a surrogate marker of bleeding and recurrence risk, with the secondary outcome measures of major bleeding and VTE recurrence at 30 days.
Methods: A 5-year retrospective audit of patients with acute VTE who were prescribed enoxaparin at 1mg/kg BD, with an anti-Xa level taken 2-6 hours post-dose. Patients with an eGFR <30 were excluded.
Results: 166 patients weighing >100kg with acute VTE were identified, and 63 were excluded for not fulfilling all criteria. 64 patients weighing <100kg were assessed for comparison. Table 1 describes the patient characteristics, anti-Xa levels and clinical outcomes for patient above and below 100kg. Figure 1 demonstrates the anti-Xa levels in group 1 according to weight, and the distribution of anti-Xa levels below, within and above the therapeutic range (0.5-1.0U/mL).
Discussion: Patients above and below 100kg dosed with 1mg/kg enoxaparin BD showed no significant difference in either median anti-Xa levels, or distribution of anti-Xa activity. Regardless of weight, the majority of patients with an eGFR of 30-59 mL/min had anti-Xa levels >1.0U/mL. The obese patients did not suffer any major bleeding or VTE recurrence within 30 days. In comparison, the patients weighing <100kg, despite similar levels of anticoagulation, had higher rates of bleeding and recurrence. This was likely due to their older age and comorbidities, particularly renal impairment and concurrent cancer. These findings are consistent with the observation that bleeding risk is primarily determined by clinical characteristics rather than the anti-Xa activity alone.
Conclusion: These data support a weight-based dosing strategy for enoxaparin in obese patients with VTE, with no dose-capping, to ensure therapeutic drug levels. Routine anti-Xa levels in patients weighing >100kg, particularly in those with moderate renal impairment, allow tailoring of doses to the therapeutic anti-Xa range.
Reference:
(1) Martin K et al. Use of the direct oral anticoagulants in obese patients: guidance from the SSC of the ISTH. Journal of thrombosis and haemostasis 2016; 14: 1308-13.
No relevant conflicts of interest to declare.
