Are There Potential Predictors for Response to Enoxaparin in the Neonatal Population?.

The recognition of thromboembolic events (TE) in the pediatric population is increasing. Recently, effort has been directed at determining the correct dosing of low molecular weight heparins necessary to achieve the therapeutic heparin concentration. It has been noted by our group and others that a higher dose of enoxaparin is required for the neonatal population than was originally proposed in the literature. Currently, the reason for this is not understood. Retrospectively, we examined our population of neonates for possible factors that may affect the dose requirements: the presence of sepsis (sepsis is felt to increase the need of heparin by an as yet unknown mechanism), level of antithrombin (AT; it is the protein whose action is accelerated by the presence of heparin and is normally low in the neonate), FVIII (elevated levels >200% have been associated with increased risk of TE) and fibrinogen (an acute phase reactant).

Results: Twenty-five neonates were treated with subcutaneous enoxaparin for venous and arterial TE over a two year period. A total of 84% (21/25), had antithrombin (AT), Factor VIII and fibrinogen levels measured. All AT levels were drawn at the time of diagnosis, prior to initiating enoxaparin. The majority of, but not all, FVIII and fibrinogen levels were drawn at diagnosis. A starting dose of at least 1.6 mg/kg/dose of enoxaparin was received by 18/25 (72%). Therapeutic heparin levels (0.5 –1.0 aXa units/mL) at first measure were achieved in 12/18 (67%) patients. The range of enoxaparin dosages needed to achieve therapeutic heparin levels was 1.42–2.2 mg/kg/dose. The above factors were each compared to the dosage (mg/kg) required to attain a therapeutic heparin concentration. None of these factors appeared to clearly predict for a higher enoxaparin dosage in our population. It is interesting to note that those patients with sepsis seem to need a higher than usual dosage of enoxaparin to achieve a therapeutic heparin level. However, the number of patients in this group is too few to verify this observation.

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. AT levels at the beginning of therapy, as well as FVIII and fibrinogen levels, are not predictive of the need for higher dosage requirements of low molecular weight heparin in the newborn. A greater number of patients are necessary to substantiate the observation that sepsis may be an important predictor of initial enoxaparin dosage in the neonatal population.