C. J. Pannucci1, K. I. Fleming1, A. Prazak2, C. Bertolaccini2, B. Pickron3 1University Of Utah,Division Of Plastic Surgery,Salt Lake City, UT, USA 2University Of Utah,Department Of Pharmacy,Salt Lake City, UT, USA 3University Of Utah,Department Of Surgery,Salt Lake City, UT, USA
Introduction:
Colorectal surgery patients, particularly those with malignancy, are known to be at increased risk for post-operative venous thromboembolism (VTE). Current recommendations support that enoxaparin prophylaxis minimizes risk for peri-operative VTE. While enoxaparin 40mg once daily is a commonly prescribed prophylactic dose, whether this dose adequately thins the blood remains unknown—this is relevant because inadequate enoxaparin dose has been associated with downstream VTE events in other surgical populations. We examined anti-Factor Xa (aFXa) levels, a marker of blood thin-ness, in response to enoxaparin 40mg once daily among a prospectively recruited cohort of colorectal surgery patients.
Methods:
Colorectal surgery patients were prospectively enrolled into this clinical trial (NCT02704052). Patients received enoxaparin 40mg once daily, initiated at 6-18 hours after their surgical procedure. Peak and trough aFXa levels were drawn, with goals of 0.3-0.5 IU/mL and 0.1-0.2 IU/mL, respectively; these ranges have been shown to maximize VTE risk reduction while minimizing bleeding risk. We examined the proportion of patients with in and out of range aFXa in response to enoxaparin 40mg once daily and the impact of patient weight on rapidity of enoxaparin metabolism.
Results:
To date, 39 colorectal surgery patients who received enoxaparin 40mg once daily have been enrolled. One patient had post-operative rectal bleeding requiring enoxaparin cessation prior to aFXa lab draws. 63.2% of patients (n=24) had inadequate peak aFXa levels (<0.3 IU/mL) in response to enoxaparin 40mg once daily. 28.9% of patients (n=11) had in range peak aFXa levels (0.3-0.5 IU/mL) and 7.9% of patients (n=3) were over-anticoagulated (>0.5 IU/mL). Patient weight was associated with rapidity of enoxaparin metabolism (r2=0.41). Among 22 patients who had trough levels drawn, 81.8% (n=18) had an undetectable trough level at 12 hours—thus the majority of patients actually receive no chemical prophylaxis for 12 hours per day.
Conclusion:
Based on pharmacodynamics, enoxaparin 40mg once daily is inadequate for the majority of colorectal surgery patients. For a medication that is administered daily, four out of five colorectal surgery patients receive no detectable anticoagulation for 12 hours per day. This study plans to continue patient accrual for one year, with the goal of correlating aFXa with clinically relevant endpoints including 90-day VTE and 90-day bleeding. As patient weight predicts rapidity of enoxaparin metabolism, a weight-based enoxaparin dosing strategy might be more appropriate.
