Evaluation of Risk Factors for Supratherapeutic Anti-Xa Levels with Treatment-Dose Enoxaparin in Hospitalized Patients Without Severe Renal Impairment

The standard dose of enoxaparin for therapeutic anticoagulation is 1 mg/kg every 12 h in patients with a creatinine clearance (CrCl) greater than 30 mL/min. Besides pregnancy, obesity, and renal impairment, literature on other risk factors for supratherapeutic anti-Xa levels is sparse. The objective of this retrospective study was to determine novel risk factors for supratherapeutic anti-Xa levels and further inform empiric enoxaparin dosing. We included adult patients with CrCl greater than 30 mL/min that received 1 ± 0.09 mg/kg of enoxaparin every 12 h. The primary outcome was the correlation between blood urea nitrogen (BUN) and anti-Xa levels. The associations between other clinical factors and supratherapeutic anti-Xa levels were also evaluated. Secondary outcomes included the incidence of major bleeding and breakthrough thrombosis in patients who had supratherapeutic levels versus those who did not. A total of 732 patients were included in the final analysis. A small correlation was detected between BUN and anti-Xa levels (Pearson correlation coefficient 0.25, P <. 001). However, multivariate analyses revealed that only female sex, body mass index, number of enoxaparin doses prior to the initial anti-Xa level, concomitant corticosteroid administration, and lower CrCl were associated with an increased risk of supratherapeutic levels (P <. 05) when controlling for other factors. There were no significant differences in the incidence of major bleeding or breakthrough thrombosis in patients with supratherapeutic, therapeutic, or subtherapeutic levels. In this study, we identified potential risk factors for supratherapeutic anti-Xa levels in patients without severe renal impairment that may be clinically relevant when empirically dosing therapeutic enoxaparin.