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

Pannucci, Christopher J., M.D., M.S.; Fleming, Kory I., M.P.H.; Agarwal, Jayant, M.D.; Rockwell, W. Bradford, M.D.; Prazak, Ann Marie, Pharm.D., B.C.P.S.; Momeni, Arash, M.D.

Plastic and Reconstructive Surgery: July 2018 - Volume 142 - Issue 1 - p 239-249
doi: 10.1097/PRS.0000000000004517
Plastic Surgery Focus: Special Topics
Journal Club
Patient Safety CME

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.


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Salt Lake City, Utah; and Palo Alto, Calif.

From the Divisions of Plastic Surgery, Health Services Research, and Pharmacy, University of Utah; and the Division of Plastic and Reconstructive Surgery, Stanford University.

Received for publication August 23, 2017; accepted December 29, 2017.

This trial is registered under the names “Enoxaparin Metabolism in Reconstructive Surgery Patients,” identification number NCT02411292 (; and “Twice Daily Enoxaparin Prophylaxis in Reconstructive Surgery Patients,” identification number NCT02687204 (

Disclosure:None of the authors has a financial interest in any of the products, devices, or drugs mentioned in this article.

By reading this article, you are entitled to claim one (1) hour of Category 2 Patient Safety Credit. ASPS members can claim this credit by logging in to Dashboard, clicking “Submit CME,” and completing the form.

This work was supported by THE PLASTIC SURGERY FOUNDATION.

Christopher J. Pannucci, M.D., M.S., Division of Plastic Surgery, Division of Health Services Research, University of Utah, Salt Lake City, Utah 84132,

Copyright © 2018 by the American Society of Plastic Surgeons