The Impact of Once- versus Twice-Daily Enoxaparin Prophylaxis on Risk for Venous Thromboembolism and Clinically Relevant Bleeding

BACKGROUND: Venous thromboembolism is a life- or limb-threatening complication that occurs in plastic surgery patients. At present, the optimal dose of enoxaparin that balances the risk of venous thromboembolism and the risk of medication-related adverse drug events-specifically, bleeding-remains unknown. METHODS: This study compared pharmacodynamic and clinical outcomes, including 90-day venous thromboembolism and 90-day clinically relevant bleeding, between two prospectively performed clinical trials whose sole difference was postoperative anticoagulation strategy. Patients in trial 1 received enoxaparin 40 mg once daily for the duration of inpatient stay, and patients in trial 2 received enoxaparin 40 mg twice daily for the duration of inpatient stay. The study also examined the potential impact of a weight-based twice-daily prophylaxis strategy to achieve in-range anti-factor Xa levels. RESULTS: The study compared 94 patients who received once-daily enoxaparin to 118 patients who received twice-daily enoxaparin. Twice-daily enoxaparin was associated with a significant decrease in 90-day acute venous thromboembolism (0 percent versus 5.3 percent; p = 0.012) and a nonsignificant increase in 90-day clinically relevant bleeding (6.8 percent versus 3.2 percent; p = 0.25). Twice-daily enoxaparin at 0.4 to 0.5 mg/kg may allow an increased proportion of patients to avoid both inadequate anticoagulation and overanticoagulation, based on anti-factor Xa levels. CONCLUSIONS: Twice-daily enoxaparin is superior to once-daily enoxaparin for 90-day acute venous thromboembolism risk reduction. Twice-daily enoxaparin may increase clinically relevant bleeding, although observed differences in this study were not significant. Weight-based twice-daily enoxaparin dosing may optimize the risks and benefits of prophylactic anticoagulation after plastic and reconstructive surgery. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, II.