Enoxaparin Dose Requirements to Achieve Therapeutic Low–molecular-weight Heparin Anti-factor Xa Levels in Infants and Young Children

Abstract

Introduction: Enoxaparin is commonly used to treat pediatric thrombosis. Several small retrospective studies have suggested that infants and young children require higher enoxaparin doses to achieve therapeutic anti-factor Xa levels compared with adults. Materials and Methods: This is a retrospective study of hospitalized children who received enoxaparin for the treatment of thrombosis at a free-standing children’s hospital. The primary objective was to ascertain the enoxaparin dose required to achieve an anti-factor Xa level of 0.5 to 1.0 U/mL among 4 age groups in a large cohort of infants and young children between 60 days and 5 years of age. Results: A total of 176 infants and children were evaluated. The majority of patients were less than 1 year of age (n=104). An inverse relationship between enoxaparin dose needed to achieve therapeutic anti-factor Xa levels and patient age was noted, particularly in the first year of life. Patients who were 60 days to less than 7 months at the time of enoxaparin initiation (n=73) required the highest mean dose among the age groups at 1.73 mg/kg subcutaneously every 12 hours (P<0.0001). Conclusion: Infants and young children require higher doses of enoxaparin to achieve therapeutic anti-factor Xa levels compared with adults.

Evaluation of Initial Enoxaparin Dosing and Antifactor Xa Levels in Infants Admitted to the Neonatal Intensive Care Unit

“…Fifty-three percent of patients did not achieve a therapeutic antifactor Xa level after the first dose, and cumulatively, 71% of the preterm or low birth weight neonates achieved subtherapeutic antifactor Xa levels after initial doses. These findings are consistent with our findings and results from other studies, which indicate a need for higher initial doses of enoxaparin in infants than what is currently recommended to minimize excessive dose adjustments [2‒4, 7‒10, 12‒15].…”

“…Clearance of enoxaparin is traditionally higher in infants compared to older children and adults, which in turn, leads to requiring an increased dose [9]. Due to the differences in pharmacokinetic parameters in this patient population, close monitoring of antifactor Xa levels is recommended [7‒10, 14]. Another factor that could be adding to the need for a higher dose may include the characteristically low levels of AT3 in infants.…”

Paediatric medicine issues and gaps from healthcare workers point of view: survey results and a narrative review from the global accelerator for paediatric formulations project

“…Indeed, dosing adaptation is needed, especially for overweight or obese children ( Derbalah et al, 2022 ) as well as for infants and young children who require higher enoxaparin doses than adults to achieve therapeutic anti-factor Xa levels ( Wysocki et al, 2021 ).…”

Thromboembolic complications in newborns – diagnostic value of D-dimers concentration and proposed outline of enoxaparin use

“…for the use of EX include hypersensitivity to EX, HP or its derivatives, including other LMWHs or any of its components, a history of immune heparin thrombocytopenia (HIT) within the last 100 days or the presence of circulating antibodies, active clinically significant bleeding, ulceration stomach or intestines, perforation of the gastrointestinal tract, presence of a malignant tumour with a high risk of bleeding, recent surgery of the brain, spinal cord or eye, diagnosis or suspicion of oesophageal varices, anatomical abnormalities in the cvardio-vascular system, vascular aneurysms or serious abnormalities of blood vessels in the spinal cord or brain, IVH III and IV grade in the Papille's classification, simultaneous use of Ibuprofen, time less than 6 hours from lumbar puncture (LP), severe, untreated and life-threatening metabolic disorders, such as hyperkalaemia, metabolic acidosis, hyperglycaemia, end-stage renal failure without dialysis, and concomitant use of thrombolytic therapy (TT) [79][80][81][82][83].…”