If some is good, more is better: An enoxaparin dosing strategy to improve pharmacologic venous thromboembolism prophylaxis

Abstract

BACKGROUND Empiric enoxaparin dosing is inadequate for most trauma patients, leading to below target initial anti-Xa levels and requiring dose adjustment for optimal venous thromboembolism prophylaxis. We hypothesize that patient factors affecting initial anti-Xa levels can be identified based on drug pharmacokinetics, allowing creation of a new dosing protocol that will provide a higher percentage of in-target (0.2-0.4 IU/mL) patients at initial anti-Xa level assessment. METHODS Records of 318 trauma patients were evaluated, and NONMEM and PSN software were used to analyze 11 variables for their effects on anti-Xa levels. Computer modeling was used to select a new dosing protocol, which was implemented on the trauma service as a quality improvement project. The first 145 patients appropriately enrolled were assessed for response and complications. RESULTS Only 29.5% of the pre-intervention group had initial anti-Xa levels in the appropriate prophylactic range (Fig. 1). Levels were most strongly influenced by patient weight, outweighing contributions from all other variables. A new regimen for initial dosing was therefore designed with three weight-defined categories for ease of administration. The post-intervention group showed an increase in in-target initial anti-Xa levels to 74.5% (p < 0.001), with a corresponding decrease in subprophylactic patients from 68.0% to 20.7%. There was an increase in supraprophylactic levels to 4.8%, but no supraprophylactic patients had hemorrhagic complications. Figure 1 Percentage of patients below, in, and above target anti-Xa levels, by dosing regimen. ∗Difference pre-intervention to new dosing regimen p < 0.05. CONCLUSIONS Implementation of a new, categorized, weight-based enoxaparin dosing protocol was safe and significantly improved the percentage of trauma patients with in-target anti-Xa levels on initial assessment. Further studies are needed to determine whether such dosing decreases venous thromboembolism rates.