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Inadequate Enoxaparin Dosing Predicts 90-Day Venous Thromboembolism Risk among Plastic Surgery Inpatients: An Examination of Enoxaparin Pharmacodynamics

Pannucci, Christopher J. M.D., M.S.; Rockwell, W. Bradford M.D.; Ghanem, Maureen Pharm.D.; Fleming, Kory I. M.P.H.; Momeni, Arash M.D.; Agarwal, Jayant M.D.

Plastic & Reconstructive Surgery: April 2017 - Volume 139 - Issue 4 - p 1009–1020
doi: 10.1097/PRS.0000000000003159
Special Topic

Background: Evidence-based plastic surgery guidelines support the effectiveness of once-daily enoxaparin prophylaxis. Despite prophylaxis, one in 25 highest risk patients has a venous thromboembolism event. The authors examined the pharmacodynamics of standard enoxaparin doses in plastic surgery patients to examine whether patient-level factors predict enoxaparin metabolism, whether inadequate enoxaparin dose predicts downstream venous thromboembolism events, and whether a pharmacist-driven dose-adjustment protocol was effective.

Methods: The authors recruited adult plastic surgery patients who received postoperative enoxaparin at 40 mg/day. Steady-state peak anti–factor Xa levels, a marker of enoxaparin effectiveness and safety, were determined. Patients with out-of-range anti–factor Xa levels had real-time dose adjustment based on a written protocol. Patients were followed for 90-day venous thromboembolism events.

Results: Ninety-four patients were recruited, and 44 percent had in-range peak anti–factor Xa levels in response to standard enoxaparin dosing. Patient-level factors including extent of surgical injury and gross weight were independent predictors of enoxaparin metabolism. Patients with low anti–factor Xa levels were significantly more likely to have 90-day venous thromboembolism (10.2 percent versus 0 percent; p = 0.041). Real-time dose adjustment allowed a significantly increased proportion of patients to have in-range levels (67.1 percent versus 44.3 percent; p = 0.002).

Conclusions: Based on pharmacodynamic data, the majority of plastic surgery patients receive inadequate enoxaparin prophylaxis using fixed dosing. Patient-level factors can predict how patients will metabolize enoxaparin, and patients who receive inadequate enoxaparin prophylaxis are significantly more likely to have downstream venous thromboembolism events. Individualization of enoxaparin prophylaxis may minimize perioperative venous thromboembolism risk and further improve patient safety after plastic and reconstructive surgery procedures.

CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, II.

Salt Lake City, Utah; and Philadelphia, Pa.

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

Received for publication June 14, 2016; accepted August 31, 2016.

This trial is registered under the name “Enoxaparin Metabolism in Reconstructive Surgery Patients,” clinicaltrials.gov identification number NCT02411292 (https://clinicaltrials.gov/ct2/show/NCT02411292).

These data were presented at the 95th Annual Meeting of the American Association of Plastic Surgeons, in New York, New York, May 19 through 22, 2016.

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

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, christopher.pannucci@hsc.utah.edu

©2017American Society of Plastic Surgeons