The impact of once versus twice daily enoxaparin prophylaxis on risk for venous thromboembolism and clinically relevant bleeding

Introduction: Venous thromboembolism (VTE) 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 VTE and the risk of medication related adverse drug events, specifically bleeding, remains unknown. Methods: This study compared pharmacodynamic and clinical outcomes, including 90-day VTE and 90-day clinically relevant bleeding, between two prospectively performed clinical trials whose sole difference was post-operative anticoagulation strategy. Patients in Trial #1 received enoxaparin 40mg once daily for the duration of inpatient stay, and patients in Trial #2 received enoxaparin 40mg 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 VTE (0% vs. 5.3%, p=0.012) and a non-significant increase in 90-day clinically relevant bleeding (6.8% vs. 3.2%, p=0.25). Twice daily enoxaparin at 0.4-0.5mg/kg may allow an increased proportion of patients to avoid both inadequate anticoagulation and over-anticoagulation, based on anti-Factor Xa levels. Conclusion: Twice daily enoxaparin is superior to once daily enoxaparin for 90-day acute VTE 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 & reconstructive surgery. Meeting Disclosure: These data have not been presented. Financial disclosure page: None of the authors has a financial interest in any of the products, devices, or drugs mentioned in this manuscript. Funding for this study was provided by the Plastic Surgery Foundation (National Endowment for Plastic Surgery grant, to CJP) and the Agency for Healthcare and Research Quality's R03 mechanism (1 R03 HS024326, to CJP). Dr. Pannucci also receives research support from the American Association of Plastic Surgeon's AAPS/PSF Academic Scholar Award. CLINICAL TRIAL IDENTIFIER: Studies registered on clinicaltrials.gov: NCT02411292 and NCT02687204 ACKNOWLEDGEMENTS: Funding for this study was provided by the Plastic Surgery Foundation (National Endowment for Plastic Surgery, to CJP) and the Agency for Healthcare and Research Quality (1 R03 HS024326, to CJP). Dr. Pannucci also receives research support from the American Association of Plastic Surgeon's AAPS/PSF Academic Scholar Award. Corresponding Author: Christopher J. Pannucci, MD MS, Assistant Professor, Division of Plastic Surgery, Division of Health Services Research, University of Utah, 801 581 7719 (phone), 801 581 5794 (fax), Christopher.Pannucci@hsc.utah.edu ©2018American Society of Plastic Surgeons