Heparin Clearance in the Newborn

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Abstract
Summary: Twenty-five preterm newborns were given bolus infusions of sodium heparin (100 units/kg) and plasma heparin levels were assayed at 5, 20, 40, 90, and 150 min. Eight normal adults received a 75 units/kg bolus of heparin and levels were assayed at 5, 30, 60, 120, 180, and 240 min. In comparison with the adult data (mean adult plasma heparin half life (T1/2) = 63.3 min), the newborn infants demonstrated a significantly shorter plasma heparin half life (T1/2 = 35.5 min in group I, 33 to 36 wk gestation; 35.5 min in group II, 29 to 32 wk gestation; and 41.6 min in group III, 25 to 28 wk gestation), as demonstrated by a chromogenic heparin assay. The newborn groups had a larger volume of distribution (Vd) of heparin which varied inversely with gestational age (Vd = 36.6 ml/kg in the adults, 57.8 ml/kg in group I, 73.3 ml/kg in group II, and 81.0 ml/kg in group III babies. Heparin clearance (Cl) was significantly greater in all newborn groups when compared with the adult (ClAdult = 0.43 ml/kg/min; ClGrI = 1.37 ml/kg/min; ClGrII = 1.43 ml/kg/min; and ClGrIII = 1.49 ml/kg/min). A one-stage clotting assay for heparin generated similar results, although infant plasma heparin levels were slightly higher by this assay. Before heparin administration, the mean antithrombin III antigen (AT-III Ag) of the babies was 26.5% of normal adult and was not further decreased 90 min after the heparin bolus. Speculation: The larger volume of distribution of heparin could require a greater loading dose per kg body weight to achieve a desired plasma level and the more rapid plasma clearance could necessitate higher infusion rates to maintain a desired plasma heparin level in newborn infants. The authors speculate that the study findings are the additive result of the more rapid metabolic rate of the newborn and the physiologically low circulating levels of antithrombin 111.