Inadequate Enoxaparin Dosing Predicts 90-Day Venous Thromboembolism Risk among Plastic Surgery Inpatients: An Examination of Enoxaparin Pharmacodynamics.

BACKGROUND: Evidence-based plastic surgery guidelines support the effectiveness of once-daily enoxaparin prophylaxis. Despite prophylaxis, one in 25 highest risk patients has a venous thromboembolism event. The authors examined the pharmacodynamics of standard enoxaparin doses in plastic surgery patients to examine whether patient-level factors predict enoxaparin metabolism, whether inadequate enoxaparin dose predicts downstream venous thromboembolism events, and whether a pharmacist-driven dose-adjustment protocol was effective. METHODS: The authors recruited adult plastic surgery patients who received postoperative enoxaparin at 40 mg/day. Steady-state peak anti-factor Xa levels, a marker of enoxaparin effectiveness and safety, were determined. Patients with out-of-range anti-factor Xa levels had real-time dose adjustment based on a written protocol. Patients were followed for 90-day venous thromboembolism events. RESULTS: Ninety-four patients were recruited, and 44 percent had in-range peak anti-factor Xa levels in response to standard enoxaparin dosing. Patient-level factors including extent of surgical injury and gross weight were independent predictors of enoxaparin metabolism. Patients with low anti-factor Xa levels were significantly more likely to have 90-day venous thromboembolism (10.2 percent versus 0 percent; p = 0.041). Real-time dose adjustment allowed a significantly increased proportion of patients to have in-range levels (67.1 percent versus 44.3 percent; p = 0.002). CONCLUSIONS: Based on pharmacodynamic data, the majority of plastic surgery patients receive inadequate enoxaparin prophylaxis using fixed dosing. Patient-level factors can predict how patients will metabolize enoxaparin, and patients who receive inadequate enoxaparin prophylaxis are significantly more likely to have downstream venous thromboembolism events. Individualization of enoxaparin prophylaxis may minimize perioperative venous thromboembolism risk and further improve patient safety after plastic and reconstructive surgery procedures. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, II.

Enoxaparin and antifactor Xa levels in pediatric acute burn patients.

Previous work from the authors' group showed a risk for inadequate enoxaparin dosing for venous thromboembolism prophylaxis in adult burn patients when traditional recommendations are used. The purpose of this study was to determine whether this also applied to pediatric burn patients. Included patients were acutely burned, aged 14 years or under, and admitted to the authors' regional burn center between October 1, 2004 and December 15, 2012. Thirty-five patients included in this analysis received enoxaparin for venous thromboembolism prophylaxis dosed initially at 0.5 mg/kg and monitored with anti-factor Xa levels (anti-Xa) between 0.2 and 0.4U/ml. Of the included patients, 80% were male with a median age of 8 years, a median TBSA of 16%, and a median length of stay of 23 days. Initially 21 patients (60%) had an undetectable anti-Xa (<0.2 U/ml). Enoxaparin doses were increased but 18 patients (51%) never achieved target anti-Xa. There were no significant differences in sex, weight, dose, depth of injury, or body mass index between those who received appropriate prophylaxis and those who were undertreated. However, median size of burn was significantly larger, median age and height were significantly lower in those who did not reach target. The low number of patients achieving target prophylactic anti-Xa in this study demonstrates the need for routine anti-Xa monitoring in pediatric burns. Additionally, pediatric patients with major burn injury may require initial dosing of enoxaparin greater than published recommendations because of altered pharmacokinetics.

Evaluation of an enoxaparin dosing calculator using burn size and weight.

Previous research has shown that inadequate antifactor Xa levels (anti-Xa) occur in burn patients and may increase the risk of venous thromboembolic events (VTE). The objective of this retrospective review was to investigate the usefulness of an enoxaparin dosing algorithm using a previously published equation. With institutional review board approval, all acute burn patients at an American Burn Association-verified regional burn center who were treated with enoxaparin for VTE prophylaxis and had at least one anti-Xa from May 1, 2011 to December 15, 2012 were included. Patients with subprophylactic anti-Xa received increased enoxaparin dose per unit protocol with the goal of obtaining a prophylactic anti-Xa (0.2-0.4 U/ml). Sixty-four patients were included in our analysis. The regression equation was used in 33 patients for initial enoxaparin dosing (Eq) whereas 31 patients received traditionally recommended prophylaxis dosing (No-Eq). Groups were comparable in sex, age, weight, inhalation injury, and burn size. Initial enoxaparin dosing in Eq was significantly more likely to reach target than in No-Eq (73 vs 32%; P = .002). No episodes of hemorrhage, thrombocytopenia, or heparin sensitivity were documented in either group. Median final enoxaparin dose required to reach prophylactic level was 40 mg every 12 hours (range, 30-80 mg). Twenty-one No-Eq patients ultimately reached target, and 11 of these final doses were equivalent to or greater than the predicted equation. Ten patients never reached prophylactic anti-Xa before enoxaparin was discontinued (nine from No-Eq). Two patients, one from each group, developed VTE complications despite appropriate anti-Xa for prophylaxis. A strong correlation was shown between weight, burn size, and enoxaparin dose (r = .68; P < .001). Use of the enoxaparin dosing algorithm significantly increased the frequency of obtaining a target initial anti-Xa. There were no bleeding complications. Enoxaparin dosing correlates to burn size and weight, making a standard dose inappropriate because patient habitus and extent of burn injury are highly variable. This simple equation improves enoxaparin dosing for acute adult burn patients.