Evaluation of enoxaparin dosing requirements in infants and children

Bauman, Mary E.; Belletrutti, Mark; Bajzar, Laszlo; Black, Karina L.; Kuhle, Stefan; Bauman, Michelle L.; Massicotte, M. Patricia

doi:10.1160/th08-03-0148

Cited by 62 publications

(9 citation statements)

References 27 publications

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“…Low-molecular-weight heparin median doses in <3 month old subjects are consistent with recently revised dosing recommendations. 12 The AA % inhibition and ADP NetG were used to determine the initiation and modification of antiplatelet agent dosing. Multiple factors ( e.g.…”

Section: Discussionmentioning

confidence: 99%

Antithrombotic Therapy in a Prospective Trial of a Pediatric Ventricular Assist Device

2016

ASAIO Journal

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Efficacious ventricular assist device (VAD) support in pediatric patients depends on successful antithrombotic management. The experience with antithrombotic management for the EXCOR Pediatric VAD Investigational Device Exemption (IDE) study is described. All 68 children in North America enrolled in the IDE study from May 9, 2007 to December 10, 2010 are included. The Edmonton Anticoagulation and Platelet Inhibition Protocol was provided for management guidance. Monitoring parameters, drug dosing, targeted serious adverse events, and pump changes were reviewed. Major bleeding occurred in 43% of all subjects with most events occurring within 14 days of implantation. Bleeding events were probably/definitely related in 24% to antithrombotic management. Neurologic events occurred in 28% of subjects and were probably/definitely related in 9% to antithrombotic therapy intensity. Most neurologic events occurred between 4 and 30 days postimplantation and sporadically thereafter. Pump change occurred in 56% of subjects. Use of an antithrombotic protocol for enrolled subjects was possible in this multicenter study. Incidence of significant bleeding and thromboembolic events was acceptable when balanced against life-saving benefits of VADs. Further studies are needed to optimize the antithrombotic management of this patient population.

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Section: Discussionmentioning

confidence: 99%

Antithrombotic Therapy in a Prospective Trial of a Pediatric Ventricular Assist Device

2016

ASAIO Journal

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“…Nevertheless, almost all patients required gradual increases in enoxaparin dosage, a process that took several days. Our finding that patients of low postmenstrual age require even higher doses of enoxaparin is novel; although prior studies have examined enoxaparin dosing in NICU patients as a function of chronological or gestational age, they have not combined the two 11, 21, 22 . By accounting for maturation of an infant’s vasculature and physiology before and after birth, postmenstrual age may better identify overall maturity than either gestational or chronological age alone.…”

Section: Discussionmentioning

confidence: 99%

“…In recent years, anticoagulation with LMWH has become relatively standardized through the American College of Chest Physicians’ (ACCP) guidelines for anticoagulation 10 . A growing body of evidence shows that preterm neonates require higher doses of LMWH to achieve anti-factor Xa levels within target ranges 10, 11, 12, 13, 14, 15 . However, in the absence of large randomized controlled trials, and with much of our current understanding of pharmacokinetics extrapolated from adult studies, ideal dosing for anticoagulation in critically ill neonates remains uncertain 13, 16, 17, 18 .…”

Section: Introductionmentioning

confidence: 99%

Treatment and follow-up of venous thrombosis in the neonatal intensive care unit: a retrospective study

et al. 2016

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ObjectiveThe critically ill, premature patients of neonatal intensive care units are susceptible to venous thrombosis, an adverse event associated with short- and long-term morbidity. Venous thrombosis is frequently treated with low molecular weight heparins (LMWH) such as enoxaparin, but optimal dosing of LMWH must balance the morbidity of venous thrombosis with the potential adverse affects of anticoagulation. The optimal dosing of enoxaparin for premature infants is unclear. The objective of this study was to describe enoxaparin therapy and follow-up in critically ill neonates diagnosed with venous thrombosis.Study DesignRetrospective medical record review in the neonatal intensive care unit (NICU) in a single tertiary care institution. Infants with venous thrombosis diagnosed in the NICU were identified using pre-existing quality improvement lists and medical records.ResultsTwenty-six infants with 30 venous thromboses were identified with a median gestational age of 31 weeks at birth. Eighteen (69%) infants received enoxaparin for venous thrombosis during their hospitalization, beginning with a median dose of 1.5 mg/kg every 12h. This dose was increased to a median 2.1 mg/kg every 12h to achieve target anti-factor Xa levels. The target dose was significantly higher in patients with a postmenstrual age less than 37 weeks. Enoxaparin treatment was documented after discharge in 12 patients, continuing for a median of 99 days. Four patients died during hospitalization and their deaths were not attributable to venous thrombosis or anticoagulation complication. Follow-up documentation between 6 and 24 months after venous thrombosis diagnosis revealed no major morbidity of venous thrombosis or enoxaparin therapy.ConclusionsOur data reinforces the relative safety and necessity of enoxaparin doses above 1.5 mg/kg per 12 hours in most neonates. This was particularly true for infants at lower postmenstrual age.

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“…It became evident that age has a significant influence on the effect of LMWH in sheep, as has already been demonstrated by several studies in humans [49]. Likely explanations for the low effect of sodium enoxaparin in lambs, other young animals or children are a higher volume of distribution, an increased total clearance and lower concentrations of antithrombin related to developmental haemostasis [49].…”

Section: Discussionmentioning

confidence: 99%

New aspects on efficient anticoagulation and antiplatelet strategies in sheep

et al. 2013

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BackgroundAfter addressing fundamental questions in preclinical models in vitro or in small animals in vivo, the translation into large animal models has become a prerequisite before transferring new findings to human medicine. Especially in cardiovascular, orthopaedic and reconstructive surgery, the sheep is an important in vivo model for testing innovative therapies or medical devices prior to clinical application. For a wide variety of sheep model based research projects, an optimal anticoagulation and antiplatelet therapy is mandatory. However, no standardised scheme for this model has been developed so far. Thus the efficacy of antiplatelet (acetylsalicylic acid, clopidogrel, ticagrelor) and anticoagulant (sodium enoxaparin, dabigatran etexilate) strategies was evaluated through aggregometry, anti-factor Xa activity and plasma thrombin inhibitor levels in sheep of different ages.ResultsResponses to antiplatelet and anticoagulant drugs in different concentrations were studied in the sheep. First, a baseline for the measurement of platelet aggregation was assessed in 20 sheep. The effectiveness of 225 mg clopidogrel twice daily (bid) in 2/5 sheep and 150 mg bid in 3/5 lambs could be demonstrated, while clopidogrel and its metabolite carboxylic acid were detected in every plasma sample. High dose ticagrelor (375 mg bid) resulted in sufficient inhibition of platelet aggregation in 1/5 sheep, while acetylsalicylic acid did not show any antiplatelet effect. Therapeutic anti-factor Xa levels were achieved with age-dependent dosages of sodium enoxaparin (sheep 3 mg/kg bid, lambs 5 mg/kg bid). Administration of dabigatran etexilate resulted in plasma concentrations similar to human ranges in 2/5 sheep, despite receiving quadruple dosages (600 mg bid).ConclusionHigh dosages of clopidogrel inhibited platelet aggregation merely in a low number of sheep despite sufficient absorption. Ticagrelor and acetylsalicylic acid cannot be recommended for platelet inhibition in sheep. Efficient anticoagulation can be ensured using sodium enoxaparin rather than dabigatran etexilate in age-dependent dosages. The findings of this study significantly contribute to the improvement of a safe and reliable prophylaxis for thromboembolic events in sheep. Applying these results in future translational experimental studies may help to avoid early dropouts due to thromboembolic events and associated unnecessary high animal numbers.

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Evaluation of enoxaparin dosing requirements in infants and children

Cited by 62 publications

References 27 publications

Antithrombotic Therapy in a Prospective Trial of a Pediatric Ventricular Assist Device

Antithrombotic Therapy in a Prospective Trial of a Pediatric Ventricular Assist Device

Treatment and follow-up of venous thrombosis in the neonatal intensive care unit: a retrospective study

New aspects on efficient anticoagulation and antiplatelet strategies in sheep

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