Weight-Based Enoxaparin Achieves Adequate Anti-Xa Levels More Often in Trauma Patients: A Prospective Study

Abstract

Background Previous research demonstrates that twice-daily enoxaparin is inadequate for venous thromboembolic (VTE) prophylaxis in critically ill trauma patients prompting dose adjustment based on anti-Xa levels. Most studies evaluate peak anti-Xa levels; however, data suggest that trough levels are associated with decreased VTE. We evaluated trough anti-Xa levels in noncritically ill trauma patients receiving fixed or weight-based enoxaparin. Methods Peak and trough anti-Xa levels were prospectively collected from patients receiving at least 3 consecutive doses of enoxaparin (PRE). A performance improvement project prompted a change to weight-based dosing. Peak and trough levels were subsequently prospectively collected from the weight-based group (POST). Adequate peak was defined as ≥0.2 IU/mL and adequate trough as ≥0.1 IU/mL. PRE and POST groups were compared. Results 200 patients were evaluated (100 PRE, 100 POST). In the PRE group, only 34% of trough and 61% of peak anti-Xa levels were adequate compared with 82% and 97%, respectively, in the POST group ( P < .01). Median trough improved from 0.07 IU/mL to 0.2 IU/mL ( P < .01). Median peak improved from 0.22 IU/mL to 0.47 IU/mL ( P < .01). More patients achieved adequate peak and trough levels in the POST group (79% vs 31%, P < .01). 95% of patients with adequate troughs also had adequate peaks, whereas 75% with adequate peaks had adequate troughs. Discussion Traditional enoxaparin dosing in noncritically ill trauma patients results in suboptimal anti-Xa levels. Weight-based enoxaparin improves both trough and peak anti-Xa levels obviating dose adjustment. Furthermore, troughs better predict adequate anti-Xa levels.

Relationship between anti-Xa level achieved with prophylactic low-molecular weight heparin and venous thromboembolism in trauma patients: A systematic review and meta-analysis

“…Using a weight-based enoxaparin of at least 0.5 mg/kg showed deep vein thrombosis rates and has been shown to be safe, and therefore may be of interest in future studies evaluating novel ways to adjust LMWH. 34,35 Although patients who receive VTEp and attain prophylactic anti-Xa levels are at reduced risk of developing VTE, titrating dose-adjustment strategies to achieve prophylactic anti-Xa levels paradoxically did not appear to reduce VTE rates. Dose adjustment based on anti-Xa alone may inadequately reduce VTE rates because waiting for the first anti-Xa level delays dose optimization.…”

“…[23][24][25] Despite these shortcomings, anti-Xa-based dose-adjustment protocols have been developed in critically ill, 26,27 braininjured, 28 and trauma patients, [29][30][31][32] with inconsistent results. [33][34][35] In addition, the Western Trauma Association recently published updated guidelines encouraging the initiation of VTEp within 24 hours of admission (with initial dosing based on injury profile, age, and creatinine clearance), and recommending VTEp dose titration be guided by patient weight or by anti-Xa level. 36 There is no systematic review evaluating the significance of serum anti-Xa levels on VTE in trauma patients, or evaluating outcomes from low molecular weight heparin (LMWH) doseadjusted regimens.…”

“…Similar studies in trauma patients, however, have failed to demonstrate this relationship 23–25 . Despite these shortcomings, anti–Xa-based dose-adjustment protocols have been developed in critically ill, 26,27 brain-injured, 28 and trauma patients, 29–32 with inconsistent results 33–35 . In addition, the Western Trauma Association recently published updated guidelines encouraging the initiation of VTEp within 24 hours of admission (with initial dosing based on injury profile, age, and creatinine clearance), and recommending VTEp dose titration be guided by patient weight or by anti-Xa level 36 …”

The efficacy of weight-based enoxaparin dosing for venous thromboembolism prophylaxis in trauma patients: A systematic review and meta-analysis

“…6 Overall, this acts to inhibit the common pathway of the coagulation cascade, preventing the formation of fibrin. 17 In addition, it has been demonstrated to have better bioavailability, increased anti-factor Xa (AFXa) activity, and less impact on platelets and microvascular permeability, which may result in fewer bleeding complications relative to unfractionated heparins. 18,19 The anticoagulant effect of enoxaparin has been demonstrated to be predictable in clinically stable and uncomplicated patients; 6,20 however, it can become unpredictable in other populations, 20 because of alterations in excretion, absorption, and distribution of the drug.…”

“…The improved efficacy of enoxaparin is believed to be secondary to its mechanism of action, achieving thromboprophylaxis via the binding of antithrombin to increase its inhibition of coagulation factors Xa and IIa 6 . Overall, this acts to inhibit the common pathway of the coagulation cascade, preventing the formation of fibrin 17 . In addition, it has been demonstrated to have better bioavailability, increased anti–factor Xa (AFXa) activity, and less impact on platelets and microvascular permeability, which may result in fewer bleeding complications relative to unfractionated heparins 18,19 .…”