Abstract

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)

PatientAgeWeight (kg)Indication for enoxaparinDose changesFinal dose (mg/kg)
DVT, deep venous thrombosis; CVL, central venous line 
3 months 6.5 DVT with CVL 3.8 
10 months 10 DVT with CVL 
14 months 13 DVT with CVL 2.3 
2 years 14 DVT with CVL 2.7 
3 years 14 DVT 2.7 
8 years 83 DVT with CVL 1.7 
9 years 37 Arterial ischemic stroke 1.9 
13 years 67 DVT with CVL 2.1 
14 years 65 DVT with CVL 2.2 
10 14 years 68 DVT 1.8 
11 15 years 60 DVT with CVL 1.9 
12 15 years 60 Arterial ischemic stroke 1.6 
13 15 years 77 DVT with CVL 1.5 
14 16 years 45 DVT 2.9 
PatientAgeWeight (kg)Indication for enoxaparinDose changesFinal dose (mg/kg)
DVT, deep venous thrombosis; CVL, central venous line 
3 months 6.5 DVT with CVL 3.8 
10 months 10 DVT with CVL 
14 months 13 DVT with CVL 2.3 
2 years 14 DVT with CVL 2.7 
3 years 14 DVT 2.7 
8 years 83 DVT with CVL 1.7 
9 years 37 Arterial ischemic stroke 1.9 
13 years 67 DVT with CVL 2.1 
14 years 65 DVT with CVL 2.2 
10 14 years 68 DVT 1.8 
11 15 years 60 DVT with CVL 1.9 
12 15 years 60 Arterial ischemic stroke 1.6 
13 15 years 77 DVT with CVL 1.5 
14 16 years 45 DVT 2.9 

Disclosures: The use of enoxaparin in the pediatric population is not FDA-approved. The authors obtained permission from the FDA (IND application 71,971) prior to performing this research study.; Hemophilia and Thrombosis Research Society; General Clinical Research Center, Children’s Hospital of Pittsburgh (5M01 RR00084).