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Twice-Daily Enoxaparin among Plastic Surgery Inpatients: An Examination of Pharmacodynamics, 90-Day Venous Thromboembolism, and 90-Day Bleeding

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

Plastic and Reconstructive Surgery: June 2018 - Volume 141 - Issue 6 - p 1580-1590
doi: 10.1097/PRS.0000000000004379
Plastic Surgery Focus: Special Topics
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Background: Low anti–factor Xa level, indicative of inadequate enoxaparin dosing, has a significant association with 90-day venous thromboembolism events. The authors examined the pharmacodynamics of enoxaparin 40 mg twice daily and its correlation with anti–factor Xa level, postoperative venous thromboembolism, and bleeding.

Methods: Adult patients were admitted after plastic and reconstructive surgery and received enoxaparin 40 mg twice daily. Peak anti–factor Xa levels, which quantify enoxaparin’s antithrombotic effect, were drawn, with a goal level of 0.2 to 0.4 IU/ml. Ninety-day symptomatic venous thromboembolism and clinically relevant bleeding were identified.

Results: The authors enrolled 118 patients who received enoxaparin 40 mg twice daily. Of these patients, 9.6 percent had low peak anti–factor Xa levels (<0.2 IU/ml), 62.6 percent had in-range peak anti–factor Xa levels (0.2 to 0.4 IU/ml), and 27.8 percent had high anti–factor Xa levels (>0.4 IU/ml). With enoxaparin 40 mg twice daily, 90.4 percent of patients received at least adequate prophylaxis. Patient weight predicted the rapidity of enoxaparin metabolism. Zero acute 90-day venous thromboembolism occurred. Eight patients (6.8 percent) had clinically relevant 90-day bleeding: clinical consequences ranged from cessation of enoxaparin prophylaxis to transfusion to operative hematoma evacuation.

Conclusions: When enoxaparin 40 mg twice daily is provided, 90 percent of patients receive at least adequate venous thromboembolism prophylaxis (anti–factor Xa level >0.2 IU/ml). However, 27 percent of the overall population is overtreated (anti–factor Xa level >0.4 IU/ml). These pharmacodynamics data likely explain the low rate of 90-day acute venous thromboembolism (0 percent) and the high rate of clinically relevant bleeding (6.8 percent) observed. Future studies are needed to better optimize the risks and benefits of enoxaparin prophylaxis in plastic and reconstructive surgery patients.

CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, IV.

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

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

Received for publication June 29, 2017; accepted December 6, 2017.

This study is registered under the name “Twice Daily Enoxaparin Prophylaxis in Reconstructive Surgery Patients,”clinicaltrials.gov identification number NCT02687204 (https://clinicaltrials.gov/ct2/show/NCT02687204).

Presented in part at the 60th Annual Scientific Meeting of the Southeastern Society of Plastic and Reconstructive Surgeons, in Sea Island, Georgia, June 11 through 16, 2017; and at Plastic Surgery The Meeting 2017, Annual Meeting of the American Society of Plastic Surgeons, in Orlando, Florida, October 6 through 10, 2017.

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

Christopher J. Pannucci, M.D., M.S., University of Utah Hospital, Division of Plastic Surgery, 30 North 1900 East, 3B400, Salt Lake City, Utah 84132, christopher.pannucci@hsc.utah.edu

Copyright © 2018 by the American Society of Plastic Surgeons