Enoxaparin for neonatal thrombosis: A call for a higher dose for neonates

Malowany, Janet I.; Monagle, Paul; Knoppert, David; Lee, David S. C.; Wu, John; McCusker, Patricia; Massicotte, M. Patricia; Williams, Suzan; Chan, Anthony

doi:10.1016/j.thromres.2007.11.009

Cited by 99 publications

(97 citation statements)

References 26 publications

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“…There have been no formal comparisons of doses required when an insuflon is used vs. intermittent injections so it is advisable to monitor by anti-FXa until therapeutic levels are reached. Local side effects such as bruising, induration and leakage have been described in around 10% of neonates (Malowany et al, 2008). Major local bleeding, including a case of compartment syndrome, has been reported with insuflon use in extremely low birth weight neonates (Dix et al, 2000;Streif et al, 2003;Obaid et al, 2004).…”

Section: Low Molecular Weight Heparinmentioning

confidence: 99%

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Aspects of anticoagulation in children

Payne

2010

Br J Haematol

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SummaryThe number of children receiving anticoagulation is increasing. Thromboembolic events are associated with significant risk of morbidity and mortality although the optimal management of asymptomatic events remains unclear. Specific challenges in paediatrics include the diagnosis of thrombosis, delivery and monitoring of anticoagulation in a wide range of ages from neonates through to adolescents. The development of the haemostatic system as children age results in changing pathophysiology of thrombosis and response to anticoagulation agents. Although registry and observational studies have provided vital information, specific paediatric, prospective anticoagulation studies have been few and limited in design. The result is that much of current practice is extrapolated from adult studies. Traditional anticoagulants have significant limitations. Both heparin and warfarin are in widespread use but many fundamental questions regarding dose, therapeutic range, efficacy and optimum duration have not been fully answered. Alternative agents, such as direct thrombin inhibitors and the selective anti-factor Xa inhibitor fondaparinux, may have advantages for children. Clinical trials in adults and preliminary data in children are promising but caution should be applied until specific paediatric studies have demonstrated safety and efficacy.

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Section: Low Molecular Weight Heparinmentioning

confidence: 99%

“…However, a recent overview of studies on neonates suggests a higher dose may be needed especially in preterm neonates (Malowany et al, 2008). A starting dose of 1AE7 mg/kg for term neonates and 2AE0 mg/kg for preterm neonates has been suggested where there are no additional risk factors for bleeding.…”

Section: Dosing Lmwhmentioning

confidence: 99%

Aspects of anticoagulation in children

Payne

2010

Br J Haematol

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“…Preterm infants require longer to achieve an anti-Xa level within target range compared to term infants (6 vs 2 days) and were found to require higher doses of enoxaparin (2.1 mg/kg/12 h vs 1.7 mg/kg/12 h) (Streif et al 2003). Recent evidence also suggests a starting dose of 1.7 mg/kg/12 h in term and 2 mg/kg/12 h in preterm neonates (Malowany et al 2008). Effi cacy was reported to be 59%-100%.…”

Section: Medicalmentioning

confidence: 99%

Thrombosis in the critically ill neonate: incidence, diagnosis, and management

Nold¹

2008

VHRM

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Among children, newborn infants are most vulnerable to development of thrombosis and serious thromboembolic complications. Amongst newborns, those neonates who are critically ill, both term and preterm, are at greatest risk for developing symptomatic thromboembolic disease. The most important risk factors are infl ammation, DIC, impaired liver function, fl uctuations in cardiac output, and congenital heart disease, as well as exogenous risk factors such as central venous or arterial catheters. In most clinically symptomatic infants, diagnosis is made by ultrasound, venography, or CT or MRI angiograms. However, clinically asymptomatic vessel thrombosis is sometimes picked up by screening investigations or during routine imaging for other indications. Acute management of thrombosis and thromboembolism comprises a variety of approaches, including simple observation, treatment with unfractionated or low molecular weight heparin, as well as more aggressive interventions such as thrombolytic therapy or catheter-directed revascularization. Long-term follow-up is dependent on the underlying diagnosis. In the majority of infants, stabilization of the patients' general condition and hemodynamics, which allows removal of indwelling catheters, renders long-term anticoagulation superfl uous. Nevertheless, in certain types of congenital heart disease or inherited thrombophilia, long-term prophylaxis may be warranted. This review article focuses on pathophysiology, diagnosis, and acute and long-term management of thrombosis in critically ill term and preterm neonates.

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“…125 LMWH therapy has been effective in the NICU, and centers have reported either partial or complete resolution of TE events between 59 and 100%. 125,126 The traditional initial treatment dose of enoxaparin is displayed in Table 6. A recent review evaluating enoxaparin use in 240 neonates found that the mean maintenance dose of enoxaparin ranged from 1.48 to 2.27 mg kg À1 per 12 h for all infants, but was higher for preterm neonates at 1.9 to 2.27 mg kg À1 per 12 h. 125 Therefore, newer recommendations are displayed in Table 6.…”

Section: Management Of Thrombosismentioning

confidence: 99%

The evaluation and management of postnatal thromboses

Saxonhouse

Burchfield

2009

J Perinatol

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In the pediatric population, neonates have the highest risk for thromboembolism (TE), most likely due to the frequent use of intravascular catheters. This increased risk is attributed to multiple risk factors. Randomized clinical trials dealing with management of postnatal thromboses do not exist, thus, opinions differ regarding optimal diagnostic and therapeutic interventions. This review begins with an actual case study illustrating the complexity and severity of these types of cases, and then evaluates the neonatal hemostatic system with discussion of the common sites of postnatal thrombosis, perinatal and prothrombotic risk factors, and potential treatment options. A proposed step-wise evaluation of neonates with symptomatic postnatal thromboses will be suggested, as well as future research and registry directions. Owing to the complexity of ischemic perinatal stroke, this topic will not be reviewed. Case study A full-term male infant born through spontaneous vaginal delivery was admitted to the neonatal intensive care unit (NICU) shortly after birth due to a history of low APGAR scores and respiratory distress requiring mechanical ventilation. The pregnancy was complicated by gestational diabetes treated with glyburide and chorioamnionitis was evident during labor. The patient was started on ampicillin and gentamicin and appropriate fluid resuscitation was initiated. The patient improved over the next few days and was able to be weaned off of ventilator support. The patient had an umbilical arterial catheter (UAC) placed after birth that was removed on day 3 of life.On day 4 of life the patient's legs appeared pale. Physical examination demonstrated cool lower extremities and markedly decreased pulses in the feet. Over the previous 24 h, urine output declined significantly.Ultrasound (US) examination of the heart, major vessels and abdomen demonstrated a large thrombus in the descending aorta with very minimal flow to the renal and iliac arteries. A literature search did not reveal any level I management guidelines for thrombosis in neonatal patients, and consideration is now given to surgical thrombectomy, anticoagulation therapy or fibrinolytic therapy. Incidence of neonatal thromboembolic diseaseAlthough neonates have the highest risk of thromboembolism (TE) in the pediatric population, the incidence of postnatal TE varies due to the types of thromboses that were reported and how aggressively centers screened for thromboses. 1 Data from the three international registries are displayed in Table 1. All three registries observed that thromboses occurred in both term and preterm infants and affected male and female infants equally, other than renal vein thrombosis (RVT) that affected more male neonates. [2][3][4] These registries also demonstrated that approximately 90% of venous thromboses in neonates were associated with central venous catheters (CVLs). [2][3][4] The recurrence rate of TE following symptomatic neonatal events ranges from 3.3 to 7%. 5 The international registries are the first step toward...

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Enoxaparin for neonatal thrombosis: A call for a higher dose for neonates

Cited by 99 publications

References 26 publications

Aspects of anticoagulation in children

Aspects of anticoagulation in children

Thrombosis in the critically ill neonate: incidence, diagnosis, and management

The evaluation and management of postnatal thromboses

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