Once-Daily Enoxaparin for the Treatment of Pediatric Thromboembolic Disease — A Pilot Study

Background & Aim: The current recommended starting dose of enoxaparin in children is 1 mg/kg/dose administered twice-daily. Studies in adults, however, have demonstrated similar safety and efficacy between once-daily enoxaparin (1.5 mg/kg/dose) and twice-daily (1 mg/kg/dose) in the initial and long-term treatment of venous thromboembolism. Due to known differences in heparin clearance between adults and young children, recommendations for once-daily enoxaparin dosing should not simply be extrapolated from adult literature. Our objective was to perform a pilot study to describe the pharmacodynamics of once-daily enoxaparin in children, and to gather preliminary data regarding safety and feasibility. Methods: 15 patients, ages 3 months to 16 years, with newly diagnosed thromboembolism were enrolled. All began therapy with 1.5 mg/kg enoxaparin administered once-daily. Initial peak anti-Xa levels were drawn 4–6 hours after the second dose of enoxaparin. Dose adjustments were made according to a study nomogram to achieve peak anti-Xa levels between 1–2 U/ml, as recommended by the American College of Pathologists for once-daily enoxaparin dosing. Once therapeutic levels were achieved, a subgroup of 8 patients underwent 24–hour pharmacodynamic (PD) monitoring, with anti-Xa levels drawn at Hours 0, 2, 4, 8, 12, 18, and 24. Results: 14 patients completed the study. 8 of 14 children required a final dose of >2 mg/kg to achieve target peak anti-Xa levels (Table). Only one participant (age 15 years) achieved target levels with the original dose. In PD studies, 7 of 8 children had subtherapeutic anti-Xa levels by Hour 12, and 4 of 8 had unmeasurable levels by Hour 18 (Figure). These results differ from adult studies in which therapeutic levels (0.5–1.0 U/ml) have been measurable 13–18 hours after administration, and prophylactic levels (0.1–0.3 U/ml) have been measurable at 24 hours. There were no new or recurrent thrombotic events. One patient was removed from the study on Day 2 because anticoagulation was permanently discontinued after a post-surgical bleed (anti-Xa 0.23 at time of event). Conclusion: Our pilot data suggests faster clearance of once-daily enoxaparin in the pediatric population as compared to adults. The appropriate starting dose of once-daily enoxaparin in young pediatric patients is likely higher than 1.5 mg/kg. Dose adjustments needed to achieve target peak anti-Xa activity (1–2 IU/ml) Patient Age Weight (kg) Indication for enoxaparin Dose changes Final dose (mg/kg) DVT, deep venous thrombosis; CVL, central venous line 1 3 months 6.5 DVT with CVL 4 3.8 2 10 months 10 DVT with CVL 4 4 3 14 months 13 DVT with CVL 2 2.3 4 2 years 14 DVT with CVL 4 2.7 5 3 years 14 DVT 2 2.7 6 8 years 83 DVT with CVL 1 1.7 7 9 years 37 Arterial ischemic stroke 1 1.9 8 13 years 67 DVT with CVL 2 2.1 9 14 years 65 DVT with CVL 2 2.2 10 14 years 68 DVT 1 1.8 11 15 years 60 DVT with CVL 1 1.9 12 15 years 60 Arterial ischemic stroke 1 1.6 13 15 years 77 DVT with CVL 0 1.5 14 16 years 45 DVT 3 2.9 Figure Figure