Low-molecular weight heparin and dose adjustment in pediatric patients

Initial dosing for LMWH agents in pediatric patients with normal kidney function*
Drug	Therapeutic anticoagulation (for treatment of thrombosis)	Prophylaxis (for prevention of thrombosis)
Enoxaparin	Preterm neonates: 2 mg/kg/dose subQ every 12 hours Term neonates: 1.5 to 1.7 mg/kg/dose subQ every 12 hours Infants ≥2 months, children, and adolescents: 1 mg/kg/dose subQ every 12 hours^¶	Infants <2 months: 0.75 mg/kg/dose subQ every 12 hours Infants ≥2 months, children, and adolescents: 0.5 mg/kg/dose subQ every 12 hours
Dalteparin	Neonates: Limited data available; use of an alternative agent is suggested Infants and children <2 years: 150 units/kg/dose SubQ every 12 hours Children 2 to <8 years: 125 units/kg/dose SubQ every 12 hours Children >8 years and adolescents: 100 units/kg/dose SubQ every 12 hours (maximum 18,000 units/dose)	Neonates: Limited data available; use of an alternative agent is suggested Infants and children <50 kg: 100 units/kg/dose SubQ daily (maximum 5000 units/dose) Children and adolescents ≥50 kg: 5000 units SubQ daily
Nadroparin^Δ	Neonates: 150 to 180 units/kg/dose SubQ every 12 hours Infants, children, and adolescents: 86 units/kg/dose SubQ every 12 hours (maximum dose 17,100 units/day)	Infants and children <50 kg: Limited data available; use of an alternative agent is suggested Adolescents ≥50 kg: 3800 units SubQ once daily
Reviparin^Δ	Infants <5 kg: 150 units/kg/dose SubQ every 12 hours Infants and children ≥5 kg: 100 units/kg/dose SubQ every 12 hours	Infants <5 kg: 50 units/kg/dose SubQ every 12 hours Infants and children ≥5 kg: 30 units/kg/dose SubQ every 12 hours
Tinzaparin^Δ	Infants 0 to 2 months: 275 units/kg/dose SubQ daily Infants 2 to 12 months: 250 units/kg/dose SubQ daily Children 1 to 5 years: 240 units/kg/dose SubQ daily Children 5 to 10 years: 200 units/kg/dose SubQ daily (maximum 18,000 units/dose) Children and adolescents 10 to 16 years: 175 units/kg/dose SubQ daily (maximum 18,000 units/dose)	Infants and children 1 month to 17 years: 50 units/kg/dose SubQ daily
Dose titration (for therapeutic anticoagulation only)^◊
Anti-factor Xa level	Dose titration	Time to repeat anti-factor Xa level
<0.35 units/mL	Increase dose by 25%	4 hours after next dose
0.35 to 0.49 units/mL	Increase dose by 10%	4 hours after next dose
0.5 to 1 unit/mL	Keep same dose	Repeat the next day (4 hours after dose) If stable, can go to weekly monitoring
1.1 to 1.5 units/mL	Decrease dose by 20%	Before next dose
1.6 to 2 units/mL	Hold dose for 3 hours, then decrease dose by 30%	Before next dose, then 4 hours after next dose
>2 units/mL	Hold all doses until anti-factor Xa is 0.5 units/mL, then decrease dose by 40%	Before next dose and every 12 hours until anti-factor Xa is <0.5 units/mL

LMWH: low molecular weight heparin; subQ: subcutaneously.
* Dose adjustment is necessary for patients with kidney impairment. More frequent monitoring of anti-factor Xa levels may also be warranted. Refer to UpToDate topics on pediatric thrombosis for additional details.
¶ Some clinicians use slightly higher doses of enoxaparin in infants and young children (eg, for infants ages 3 to 12 months, 1.5 mg/kg/dose SubQ every 12 hours; for children ages 1 to 5 years, 1.2 mg/kg/dose SubQ every 12 hours).
Δ Nadroparin and tinzaparin are not available in the United States; reviparin is not available in most markets, including the United States.
◊ For therapeutic anticoagulation, LMWH is initiated according to the dosing guidance above and the dose is subsequently adjusted as needed to achieve anti-factor Xa levels between 0.5 and 1 units/mL in samples taken 4 to 6 hours after the last dose. The nomogram above has been most well studied in patients receiving enoxaparin; studies on dose titration using other LMWH agents in children are more limited. For prophylaxis, monitoring anti-factor Xa levels is generally not necessary; however, monitoring anti-factor Xa levels may be appropriate in select circumstances (eg, patients with kidney impairment). Refer to UpToDate topics on pediatric thrombosis for additional details.

References:

Monagle P, Chan AK, Goldenberg NA, et al. Antithrombotic therapy in neonates and children: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines. Chest 2012; 141:e737S.
Malowany JI, Monagle P, Knoppert DC, et al. Enoxaparin for neonatal thrombosis: A call for a higher dose for neonates. Thromb Res 2008; 122:826.
Kuhle S, Massicotte P, Dinyari M, et al. Dose-finding and pharmacokinetics of therapeutic doses of tinzaparin in pediatric patients with thromboembolic events. Thromb Haemost 2005; 94:1164.
Klaassen ILM, Sol JJ, Suijker MH, et al. Are low-molecular-weight heparins safe and effective in children? A systematic review. Blood Rev 2019; 33:33.
Sol J, Boerma M, Klaassen I, et al. Effectiveness and Safety of Nadroparin Therapy in Preterm and Term Neonates with Venous Thromboembolism. J Clin Med 2021; 10:1483.

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