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

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

View Large

View largeDownload slide

Figure

View largeDownload slide

Figure

Close modal