Excipients
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Pfizer ampoule: Water for injection
DBL ampoule: Hydrochloric acid, sodium hydroxide.
DBL vial: Benzyl alcohol. Do not give products that contain benzyl alcohol to neonates.
Heparinised saline: Hydrochloric acid, sodium chloride, sodium hydroxide.
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Evidence
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Efficacy
Systemic antithrombotic therapy/prophylaxis
Arterial thrombosis: Spontaneous arterial thrombosis is rare in neonates and the evidence around its management using heparin is limited to case reports only. de Godoy et al reported complete disappearance of an aortic thrombus and clinical improvement in a neonate following 15 days anticoagulation with heparin.11 Similarly, anticoagulation with heparin following initial thrombolysis of a major aortic thrombus is found to be helpful in improving clinical outcomes of neonates.12
Venous thrombosis: In a cohort of 53 neonates who received heparin, Moharir et al found significant reduction in propagation of cerebral sino-venous thrombosis (2 vs 30%; P < 0.001). However, no difference was noted in thrombus recanalisation, mortality and long term disability.13 Non-life threatening bleeding was seen in 5-6% neonates.
In two retrospective reviews involving 100 neonates who received heparin therapy for renal vein thrombosis with or without inferior vena cava involvement, there was no difference in irreversible renal damage and renal atrophy at long term follow up.14, 15 In a cohort of 128 neonates with portal vein thrombosis the incidence of lobar atrophy of liver and risk of portal hypertension was not altered by the use of anticoagulants.16
No clinical outcome studies have determined the therapeutic range for heparin in neonates and the APTT therapeutic range and monitoring is extrapolated from adults. One prospective cohort study used a weight-based nomogram to address dosing of heparin in paediatric patients required to achieve adult therapeutic APTT values. Bolus doses of 75 to 100 units/kg resulted in therapeutic APTT values in 90% of children at 4-6 hours after bolus.17
Maintenance of patency of central vascular catheters1,2, 5-7
Low dose heparin administered as a continuous infusion or regular flushes significantly increases the duration of peripheral catheter patency and reduces the episodes of infusion failure.5,6 A systematic review involving 267 neonates reported significant reduction in occlusion of peripherally placed percutaneous central venous catheters and higher rates of completion of therapy if heparin is infused at a dose of 0.5unit/kg/hr.7 Administration of heparin in low doses does not significantly alter the risk of sepsis or intraventricular haemorrhage.1,5-7 However, Lesko et. al. reported a 4-fold, but statistically not significant, increase in IVH in low-birthweight infants in a case control study (OR, 3.9; 95% CI, 1.4-11.0).10
Maintenance of patency of peripheral arterial catheters
Heparin is shown to significantly reduce clot formation and maintain patency of peripheral arterial catheter for a longer period.18 Compared with 1 unit/mL, heparin concentration of 5 units/mL is more effective in keeping arterial catheters patent for longer time.19 Studies found heparinised normal saline superior to heparinised glucose solution, and continuous infusion of heparin in normal saline better compared to intermittent flushing to improve arterial catheter patency.20,21
Safety
Major bleeding has been reported in children treated for deep vein thrombosis/pulmonary embolism. There are case reports of osteoporosis. Given the adverse effects, and the availability of alternative anticoagulants, long term use of heparin can be avoided. Heparin-induced thrombocytopenia (HIT) has been reported in neonates. Following exposure to heparin for at least 5 days, Schmugge et. al. reported antibodies against HPF4 in 2.3% children who developed thrombocytopenia and thrombosis.23 In a systematic review, Avila et. al. reported seroconversion for anti-PF4/H antibodies in 0-1.7% neonates but no neonate fulfilled the combined clinical and laboratory criteria used for the diagnosis of HIT.24
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