D. L. Jones1, A. Prazak2, K. I. Fleming3, T. Higgins1, C. J. Pannucci3 1University Of Utah,Orthopaedic Surgery,Salt Lake City, UT, USA 2University Of Utah,Salt Lake City, UT, USA 3University Of Utah,Plastic Surgery,Salt Lake City, UT, USA
Introduction:
Fixed doses of enoxaparin are routinely used in orthopaedic trauma surgery to lower the risk of perioperative venous thromboembolism (VTE). Despite prophylaxis, however, breakthrough VTE events remain high, particularly those with immobilizing lower extremity or pelvic fractures. Based on anti-Factor Xa levels (aFXa), a growing body of literature demonstrates that this “one size fits all” approach to standard enoxaparin dosing leaves a significant number of patients inadequately prophylaxed and vulnerable to VTE events. We explored enoxaparin metabolism in orthopaedic trauma patients on twice per day enoxaparin by monitoring peak and trough anti-Factor Xa (aFXa) levels as well as their association with gross weight.
Methods:
We prospectively enrolled post-operative orthopaedic trauma patients undergoing acute fracture or non-union surgery. All patients received enoxaparin prophylaxis at 30mg twice per day, initiated within 36 hours after surgery. Steady-state peak and trough aFXa levels, which measure enoxaparin effectiveness and safety, were drawn four and twelve hours after the third dose, respectively. Goal peak aFXa levels were 0.2-0.4IU/mL and goal trough levels > 0.1IU/mL. Patients with out of range peak aFXa levels had real time enoxaparin dose adjustment based on a written protocol, followed by repeat aFXa levels. Stratified analyses examined variation in peak aFXa by patient weight.
Results:
To date, 60 orthopaedic patients on 30mg twice-daily enoxaparin have been enrolled. Initial peak aFXa levels were out of range in 46.7% of patients, with 10% having undetectable levels. Trough aFXa levels were undetectable in 81.3% of patients. Dose adjustment resulted in 50% more patients reaching in-range levels. Gross weight was strongly associated with peak steady state aFXa level (Figure 1; grey box represents appropriate, in range aFXa levels). Patients with gross weight over 75 kg were significantly more likely to have inadequate aFXa levels when compared to patients ≤75 kg (63.2% vs. 13.6%, p=0.0003).
Conclusion:
Enoxaparin 30mg twice daily provided inadequately prophylaxis in nearly half of all of orthopaedic trauma surgery patients. A gross weight > 75 kilograms resulted in a significantly higher likelihood to have inadequate peak aFXa levels. Given the number of patients under-prophylaxed, inadequate enoxaparin dosing may explain some breakthrough VTE events seen in orthopaedic trauma. A weight-based enoxaparin dosing protocol may provide a more satisfactory strategy to VTE prophylaxis. Future directions aim to correlate VTE and bleeding events with peak and trough aFXa levels after orthopaedic trauma surgery and explore the effect of injury severity on predicting enoxaparin metabolism.
