Published online September 1, 2004
PEDIATRICS Vol. 114 No. 3 September 2004, pp. 703-707 (doi:10.1542/peds.2004-0178)
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Low Molecular Weight Heparin in the Treatment of Venous and Arterial Thromboses in the Premature Infant

Lisa A. Michaels, MD*, Michael Gurian*, Thomas Hegyi, MD{ddagger} and Richard A. Drachtman, MD*

* Divisions of Pediatric Hematology and Oncology
{ddagger} Neonatology, Bristol Myers Squibb Children's Hospital at Robert Wood Johnson Medical School, University of Medicine and Dentistry of New Jersey, New Brunswick, New Jersey

Objective. Thrombosis in the preterm newborn is a growing problem, a result of improved survival of the smallest and sickest infants. Treatment with low molecular weight heparin (LMWH) has potential advantages, including predictable pharmacokinetics, subcutaneous administration, and minimal monitoring. However, studies with LMWH in term infants demonstrate the need for higher doses as compared with older children and adults. Physiologic differences suggest the need for gestational age–appropriate treatment strategies. Because of the relatively small numbers of infants affected each year, large-scale prospective studies have not been feasible. With the goal of establishing treatment guidelines within our own institution, we reviewed retrospectively our experience with LMWH for the treatment of thrombosis in the preterm infant.

Methods. Medical and pharmacy records of the intensive care nursery were used to identify preterm infants with venous and arterial thrombosis. Chart documentation, orders, pharmacy records, and radiologic studies were used to develop a retrospective database to assess efficacy and safety of the treatment. Main outcome measures were the dose of LMWH required for therapeutic levels, anti-factor Xa levels achieved, bleeding complications, resolution of thrombosis, additional thromboembolic events, and death from all causes.

Results. Ten preterm infants (mean gestational age: 26 weeks) who were treated with LMWH were identified. Mean patient weight at diagnosis of thrombosis was 1215 g (range: 565–1950 g). All 10 patients had either a current or recent history of a central venous or arterial catheter. Mean starting dose of enoxaparin was 1.25 mg/kg per 12 hours (range: 0.8–2 mg/kg). Therapeutic anti-factor Xa levels were achieved in only 5 patients. Mean time to therapeutic range was 33 days (range: 14–63 days). The mean dose of enoxaparin required to achieve therapeutic levels was 2.27 mg/kg per 12 hours (dose range: 2.0–3.5 mg/kg per 12 hours). Clot resolution was observed in all but 2 patients, both of whom died of complications of their thromboembolic events. No bleeding events that necessitated a change in treatment strategy occurred.

Conclusions. Higher doses of LMWH are required in the preterm infant as compared with the healthy term neonate. Once therapeutic levels are achieved, continued regular monitoring and dose adjustments are required to maintain anticoagulation in therapeutic range.

Key Words: anticoagulation • low molecular weight heparin • enoxaparin • thrombosis • premature • neonate • low birth weight infant

Abbreviations: UFH, unfractionated heparin • ATIII, anti-thrombin III • LMWH, low molecular weight heparin • ICN, intensive care nursery • IVH, intraventricular hemorrhage

Accepted Mar 5, 2004.


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