Abstract
Heparin clearance in the newborn is more rapid than in the normal adult and anticoagulation with heparin is clinically difficult to achieve. Circulating levels of antithrombin III (AT-III) are physiologically low in term and preterm infants and minor differences in the function of AT-III in the newborn would have significant implications for the treatment of thrombosis. AT-III was isolated by heparin affinity chromatography from adult venous and newborn umbilical cord blood. The proteins thus purified were compared by SDS-PAGE, rocket immunoelectrophoresis, protein concentration by microbiuret relative to optical density at 280 nm, heparin cofactor specific activity, progressive neutralization of thrombin and factor Xa at 37° C, and pH related anti-thrombin kinetics. Finally, the reaction rates of thrombin neutralization relative to the concentration of heparin present were measured. The structural evaluations revealed a fetal AT-III molecule of molecular weight, charge and electrophoretic migration indistinguishable from that of normal adult. The functional studies showed that, on an equimolar basis, the rates of thrombin and Xa interactions with fetal AT-III were as rapid as those with adult AT-III. The catalytic rates of various concentrations of heparin were also normal. These findings suggest that “heparin resistance” in the newborn is the result of a quantitative deficiency of a normally functioning protein and support considerations for replacement therapy with AT-III.
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Mcdonald, M., Reeve, E. & Hathaway, W. 835 PURIFICATION, BIOCHEMICAL CHARACTERIZATION AND FUNCTION OF FETAL AT-III. Pediatr Res 15 (Suppl 4), 581 (1981). https://doi.org/10.1203/00006450-198104001-00860
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DOI: https://doi.org/10.1203/00006450-198104001-00860