Retrospective Analysis of the Minimum Dosage Requirements for Enoxaparin in Neonates with Thromboembolic Disease.

With advances in neonatal tertiary care, thromboembolic disease (TE) has become an increasingly recognized phenomenon. Enoxaparin, a low molecular weight heparin, is used widely in the treatment of TE in children. Current guidelines in the literature for enoxaparin therapy suggest a dosage of 1.5 mg/kg/dose every 12 hours for patients less than two months of age. However, our previous five-year retrospective review of the use of enoxaparin in the Neonatal Intensive Care Unit indicated that this dose was insufficient to achieve a therapeutic heparin level in more than 50% of the neonates studied We describe the results of initiating therapy with a higher dosage of enoxaparin.

Methods: Data were collected retrospectively from patients treated with enoxaparin subcutaneously from January 2002 to July 2004. All patients were less than three months of post-natal age at the initiation of enoxaparin therapy. TE was documented in each of the patients using radiologic studies (ultrasound, echocardiography, or CT scan).

Results: Twenty-five neonates were treated with subcutaneous enoxaparin for venous and arterial TE over a two year period. The gestational age of the neonates in the study ranged from 25–41 weeks, with 15 born before 37 weeks gestation. The neonates were treated for a variety of primary conditions, including congenital heart disease (12), complications of prematurity (9), sepsis (1), sagittal venous thrombosis (2), and one case of atypical Kawasaki disease. Radiologic investigations detected TE in the inferior vena cava (14), superior vena cava (2), aorta (3), atria (4), hepatic vein (4), sagittal vein (2), and blocked Blalock-Taussig shunt (2). Sepsis was present or suspected in 14/25 (56%) infants at the time of TE diagnosis. A total of 23 neonates (92%) received total parenteral nutrition at the time of TE. Central venous lines were in situ in 22 of 25 infants (88%). The first dosage of enoxaparin was at least 1.6 mg/kg/dose (based on actual body weight) in 18/25 (72%). Therapeutic heparin levels (0.5 –1.0 aXa units/mL) at first measure were achieved in 12/18 (67%) patients. By the time of the second measure of heparin level, 20/25 patients had dosages greater than 1.6 mg/kg/dose. Of those, 18/20 (90%) had reached a therapeutic heparin level. The dosage range to achieve a therapeutic heparin aXa was 1.42–2.2 mg/kg/dose (average 1.75 mg/kg/dose). Three infants whose doses were not maintained above 1.6 mg/kg/dose, because of weight changes, did not remain in the therapeutic range. The duration of therapy ranged from 1 to 6 months (median: 3 months). Two infants expired as a result of their primary illness. Their deaths were unrelated to the enoxaparin therapy. Three infants experienced minor bleeding while on enoxaparin.

Conclusions: Higher doses of enoxaparin are needed to treat neonates with TE. We recommend an initial dosage of enoxaparin of 1.65–1.75 mg/kg/dose based on actual body weight for neonates with TE. This is a safe and effective dosage regimen.