Adequate Anti-Xa Levels Are More Often Achieved in Trauma Patients When Dosing Enoxaparin Based on Weight

Introduction

The administration of low molecular weight heparins, such as enoxaparin, is a common part of pharmacological thromboprophylaxis in trauma patients. To monitor the effectiveness of enoxaparin therapy, the peak activity of anti-Xa and its measurement is standardly used. Previously published studies have shown that in critically ill trauma patients, standard dosing of enoxaparin is associated with insufficient anti-Xa levels.

The studies also focused on peak levels of anti-Xa; however, recent evidence suggests that trough (minimal or valley) anti-Xa values are also important for achieving adequate thromboprophylaxis. Therefore, the aim of the presented study was to evaluate the impact of standard versus weight-based dosing of enoxaparin on peak and trough anti-Xa levels in non-critically ill trauma patients.

Methodology and Study Course

The initial phase of the study included a total of 100 patients with blunt or penetrating trauma who underwent thromboprophylaxis with enoxaparin at a standard dose of 30 mg twice daily (PRE group). Trough anti-Xa activity was measured 30–60 minutes before the 4th dose of enoxaparin and peak anti-Xa activity 4 hours after the 4th dose.

Adequate peak activity was defined as ≥ 0.2 IU/ml, and trough activity as ≥ 0.1 IU/ml. Following the review of initial data, due to inadequate anti-Xa levels, enoxaparin dosing was adjusted to body weight. Another 100 patients (POST group) were prospectively evaluated with enoxaparin dosed at 0.6 mg/kg twice daily (maximum 100 mg twice daily). Peak and trough anti-Xa activities were measured in the same manner as for the PRE group.

Sequential compression devices were used for all patients except those for whom trauma characteristics prevented their use. Thromboembolic disease screening was not conducted, and only symptomatic cases were recorded.

Results

Basic demographic characteristics did not significantly differ between the groups. The median age in both groups was 48 years, with most patients experiencing blunt trauma; the PRE group had more severe injuries, while the POST group had a higher BMI. Initial creatinine values and creatinine clearance were not significantly different between groups.

In the POST group, significantly more patients had adequate trough anti-Xa levels (82 vs. 34 %; p < 0.001) and adequate peak anti-Xa levels (97 vs. 61 %; p < 0.001). The median trough anti-Xa level improved from 0.07 IU/ml in the PRE group to a therapeutic level of 0.2 IU/ml in the POST group (p < 0.001). Similarly, the median peak anti-Xa activity increased from 0.22 IU/ml in the PRE group to 0.47 IU/ml in the POST group. More patients in the POST group achieved adequate trough and peak anti-Xa activity compared to the PRE group (79 vs. 31 %; p < 0.001).

In the POST group, 21 patients exhibited supratherapeutic peak anti-Xa activity levels versus 3 in the PRE group (p < 0.001); however, no cases of severe bleeding were observed in either group. In the POST group, one patient developed upper extremity thromboembolic disease, while no TED cases were observed in the PRE group. In multivariate regression analysis controlling for BMI and creatinine clearance, weight-based dosing was the only independent predictor of achieving adequate trough anti-Xa levels (odds ratio [OR] 8.24; p < 0.001).

Conclusion

The study results suggest that trauma patients significantly more often achieve therapeutic trough and peak anti-Xa levels with weight-based dosing compared to standard dosing schemes. An unexpected correlation was also discovered: adequate peak levels did not predict adequate trough levels (only in 75 % of patients), but adequate trough levels were associated with adequate peak levels in 95 % of patients.

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Source: Stutsrim A. E., Eady J. M., Collum M. et al. Weight-based enoxaparin achieves adequate anti-Xa levels more often in trauma patients: a prospective study. Am Surg 2021; 87 (1): 77–82, doi: 10.1177/0003134820949519.