Extent of Surgical Injury Is Associated with Rate of Enoxaparin Metabolism: An Examination of Anti-Factor Xa Levels in Lower Extremity Free Flap Patients

Abstract

Venous thromboembolism is a significant cause of morbidity and mortality among surgical patients.1 Administration of a once daily or twice daily dose of enoxaparin during the perioperative period is an accepted method to prevent this life-or limb-threatening complication.2,3 However, recent studies examining multiple surgical populations have shown that a standard, "one size fits all" dose of enoxaparin does not produce sufficient levels of anticoagulation to prevent deep vein thromboembolism or pulmonary embolism in many patients. 4-7 Studies in burn patients have shown that the total body surface area (TBSA) burned is associated with rapidity of enoxaparin metabolism; patients with larger TBSA required higher doses of enoxaparin. 4,6 This is because extensive cutaneous injury produces a systemic inflammatory effect that increases drug metabolism. 4 Prior work in plastic and reconstructive surgery patients has shown that increased total body surface area surgically injured (TBSI), quantified with a Lund-Brower Chart, is associated with lower anti-factor Xa levels (aFXa); aFXa is a marker of enoxaparin activity and quantifies extent of anticoagulation. However, comparisons between patients have many confounders. The following case series examines the effect of TBSI on enoxaparin metabolism, using free flap patients as their controls. Lower extremity trauma patients who require initial debridement and later free flap surgeries can demonstrate how an increased TBSI may impact enoxaparin metabolism. Case 1A 53-year-old male marathoner and cyclist with a body mass index of 20.9 kg/m 2 presented with an extensive full-thickness wound over the lateral lower leg and ankle (►Fig. 1A).He underwent surgical debridement creating a 2% TBSI wound (►Fig. 1B). The patient was started on enoxaparin 40 mg once daily on postoperative day zero. He was enrolled in the University of Utah's clinical trial examining enoxaparin metabolism using aFXa levels (clinicaltrials.gov NCT02411292). aFXa levels were drawn as per the study protocol, and steady state peak aFXa was 0.41 IU/mL. This value was within the appropriate range of 0.3 to 0.5 IU/mL; patients in this range are considered to have blood thin enough to minimize the risk of venous thromboembolism (VTE).5,7-9 Based on our established dose-adjustment algorithm for patients who receive once daily enoxaparin, 5 no dose adjustment was made. On postoperative day 4, the patient returned to the operating room for debridement and wound coverage using a left parascapular flap-anastomoses were performed endto-side to the anterior tibial artery and end-to-end with two antegrade anterior tibial venae comitantes (►Fig. 1C). During this operation, the patient's TBSI increased to 6%. After surgery, the patient again received 40 mg of enoxaparin daily per the study protocol. Steady-state peak aFXa was 0.21 IU/mL, and this level was below the appropriate VTE prophylaxis target level of 0.3 to 0.5 IU/mL. The enoxaparin dose was increased to 50 mg once daily and repeat steady state peak aFXa was 0....