Heparin clearance and ex vivo recovery in newborn piglets and adult pigs

• Published in: Thrombosis research Vol. 52; no. 6; pp. 517 - 527
• Main Authors: Andrew, Maureen, Ofosu, Frederick, Schmidt, Barbara, Brooker, LuAnn, Hirsh, Jack, Buchanan, Michael R.
• Format: Journal Article
• Language: English
• Published: New York, NY Elsevier Ltd 15.12.1988; Elsevier Science
• Subjects: Aging - metabolism; Animals; Animals, Newborn - metabolism; Antithrombin III - isolation & purification; Antithrombin III - metabolism; Biological and medical sciences; Blood Coagulation Tests; Blood. Blood coagulation. Reticuloendothelial system; Heparin; Heparin - pharmacokinetics; Medical sciences; newborn infants; pharmacokinetics; Pharmacology. Drug treatments; piglets; Swine; pharmacokinetics; piglets; Heparin; newborn infants; Vertebrata; Mammalia; Ex vivo; Newborn animal; Adult animal; Anticoagulant; Artiodactyla; Clearance; Pharmacokinetics; Ungulata; Pig
• ISSN: 0049-3848; 1879-2472
• DOI: 10.1016/0049-3848(88)90125-9

The newborn infant requires more heparin per kg body weight than the adult to achieve similar heparin plasma levels. Possible mechanisms include altered heparin pharmacokinetics and/or a decreased expression of anticoagulant activity of heparin in newborn plasma because of low levels of antithrombin III (AT-III). We measured the pharmacokinetics and the anticoagulant activity of heparin in the pig (AT-III level:100%), in the piglet (levels of AT-III: 50% of adult) and the piglet given exogenous porcine AT-III. All pigs were bolused with 125I-heparin (25 or 100 units/kg) and blood samples collected for the measurement of 125I-radioactivity, and antifactor Xa activity. The half-life of 125I-heparin was dose-dependent and similar in pigs and piglets; however, the volume of distribution was greater in the newborn resulting in an increased total clearance compared to the pig. The anti-factor Xa activity disappeared earlier in the piglet than in the pig. Both the kinetics and the absolute recovery of anti-factor Xa activity were normalized to pig values (after correction for different volumes of distribution) when the piglets were infused with exogenous AT-III. Thus apparent heparin resistance of the newborn is due to both an increased volume of distribution and the low AT-III level which limits the measurement of the anticoagulant activity of heparin in conventional anti-factor Xa assays.