Prophylactic Enoxaparin in Critically Ill Trauma Patients: Evaluation of the Initial Dose

Abstract

Background: Trauma patients are at increased risk of developing venous thromboembolism given alterations in the coagulation cascade. Chemoprophylaxis with standard dosing of enoxaparin 30 mg subcutaneously twice daily has evolved to incorporate the use of anti-factor Xa (AFXa) trough level monitoring given concerns for decreased enoxaparin bioavailability in this patient population. Current available evidence suggests low rates of goal AFXa trough level achievement with standard enoxaparin dosing. Our study aims to identify the incidence of critically ill trauma patients that did not achieve goal AFXa trough levels and attempts to identify predictors that may influence the lack of achievement of goal levels. Methods: This was a retrospective, cohort analysis performed at a single academic medical center. Adult patients 18 years or older admitted to the surgical intensive care unit secondary to trauma who were initiated on standard prophylactic enoxaparin and had at least 1 AFXa trough level representative of steady state were included. Patient demographics and clinical data were collected, and descriptive statistics were utilized. All statistical tests were 2-tailed and a P < .05 was considered significant. Variables with a P < .10 on univariable analysis were included in a multivariable logistic regression analysis. Results: A majority of our patient population did not achieve goal AFXa trough levels while receiving standard doses of prophylactic enoxaparin (82.4% [108/131]). Sub-target AFXa levels were associated with higher creatinine clearance values. Positive predictors of obtaining target AFXa levels included automobile versus pedestrian mechanism of injury and requiring an enoxaparin dose escalation to at least 40 mg twice daily. Conclusions: Our study found low rates of achievement of goal AFXa trough levels in critically ill trauma patients receiving standard prophylactic enoxaparin dosing. Certain variables were identified as negative and positive predictors for achievement of goal AFXa trough levels, although the biologic plausibility of these predictors is questionable and requires further investigation.

Creatinine Clearance Predicts the Goal Enoxaparin Dose in Traumatic Brain Injury

“…Previous studies that have investigated the association between CrCl and enoxaparin have produced conflicting results. Subprophylactic anti-Xa levels were associated with both high and low creatinine clearance, while Malinoski et al found that subprophylactic anti-Xa levels were not associated with weight, BMI, ISS or CrCl 15–17 . However, our study differs in patient selection.…”

“…Subprophylactic anti-Xa levels were associated with both high and low creatinine clearance, while Malinoski et al found that subprophylactic anti-Xa levels were not associated with weight, BMI, ISS or CrCl. [15][16][17] However, our study differs in patient selection. Lee et al only included patients with BMI >40, while we included all patients with TBI irrespective of weight or BMI.…”

European guidelines on peri-operative venous thromboembolism prophylaxis: first update.

“…23 For trough levels, a range of 0.1 to 0.2 IU ml À1 has been proposed. 19,24 aFXa-adjusted-dose protocols have been studied, based on the peak and/or trough aFXa levels, with no clear conclusions on the preference of any of the approaches, mainly because of a lack of hard evidence on the correlation between aFXa levels and outcomes. 25 Moreover, the heterogeneity of ICU patients, the different pharmacological profiles of LMWHs and the different protocols used as standard-of-care in Europe (3500 to 4000 IU daily) vs. USA (3000 IU 12 h À1 ), 20,25,26 make an adequate interpretation and a related recommendation difficult.…”

“…Despite the administration of antithrombotic drugs (mainly LMWH) for VTE thromboprophylaxis, an excessively high rate of thrombotic events, ranging from 4 to 15% 2,3 or even higher, 1 and low rates of target antifactor Xa (aFXa) levels with standard dosing 19 have been documented.…”

“…Although the target aFXa levels range for prophylactic doses of LMWH is not well defined, due to a lack of supporting evidence, several options have been proposed for an optimal balance of efficacy and safety (both at peak and trough). Suggested target peak aFXa levels range from 0.2 to 0.4 IU ml −1 , 19,22 and even up to 0.6 in obese trauma patients 23 . For trough levels, a range of 0.1 to 0.2 IU ml −1 has been proposed 19,24 .…”