STUDY OBJECTIVE: To evaluate the effectiveness and safety of enoxaparin therapy in a neonatal intensive care unit (NICU).
DESIGN: Retrospective chart review.
SETTING: Level III NICU in a Canadian academic center.
PATIENTS: All neonates treated with enoxaparin while in the NICU between January 1, 1998, and June 1, 2006.
MEASUREMENTS AND MAIN RESULTS: Data abstracted included patient demographics, diagnosis of thrombosis and its progression, enoxaparin dosages with corresponding antifactor Xa levels, and adverse events. Sixteen neonates (four term, 12 preterm) were treated with enoxaparin at a mean +/- SD initial subcutaneous dose of 1.41 +/- 0.15 mg/kg every 12 hours. The target therapeutic range (antifactor Xa level 0.5-1.0 U/ml) was achieved by 12 infants at a mean +/- SD dose of 1.92 +/- 0.43 mg/kg every 12 hours, after a mean of 5.6 days (range 1-15 days). Preterm infants required a higher dose (per kilogram) compared with term infants to maintain therapeutic antifactor Xa levels (mean +/- SD 1.94 +/- 0.39 vs 1.65 +/- 0.14 mg/kg every 12 hrs, p<0.001). Enoxaparin doses were more strongly correlated to antifactor Xa levels in term infants (r(2)=0.51, p<0.001) compared with preterm infants (r(2)=0.20, p<0.001). Ten (71%) of 14 thromboembolic events resolved, either partially or completely, at a mean of 39 days (range 8-61 days) of enoxaparin therapy. Nine infants (56%) experienced minor local adverse effects at the site of the indwelling subcutaneous catheter (induration, bruises, hematomas, or leakage). Systemic adverse events that were possibly related to enoxaparin therapy included osteopenia (one infant), scleral hemorrhage (one), and minor gastrointestinal tract bleeding (three) found in gastric feeding tubes. No adverse effects were associated with antifactor Xa levels greater than 1.0 U/ml.
CONCLUSION: Enoxaparin may be effective in the treatment of neonatal thrombosis. An initial dosage of 1.5 mg/kg every 12 hours is likely inadequate to obtain therapeutic antifactor Xa levels rapidly and differs for term and preterm neonates. Therapeutic levels in preterm infants may be more variable, and the pharmacokinetics of this drug in preterm infants requires further evaluation. Future studies in neonates should prospectively evaluate a higher starting dose of enoxaparin to document effectiveness, acceptance, compliance with treatment guidelines, and adverse effects.