title: Standard assays underestimate the concentration of heparin in neonatal plasma.
abstract: Heparin is commonly used to treat neonatal thrombosis. Drug monitoring often involves assays that measure the inhibition of added factor Xa or thrombin by the antithrombin III (AT-III) heparin complex. We examined whether the neonatal AT-III deficiency affects heparin recovery in such assays at therapeutic drug concentrations (0.1 to 0.6 U/ml). The chromogenic anti-factor Xa assay (Teien AN, Lie M, Abildgaard U. Thromb Res 1976;8:413-6) and the protamine titration test were performed in eight pooled cord plasma samples and in normal adult plasma. Only 65% to 70% of heparin activity detected in adult plasma was recovered by the assay of Teien et al. In cord plasma; recovery by the protamine test was 80% or less. Heparin recovery in cord plasma was significantly improved by raising the AT-III concentration to normal adult levels in both assays. We conclude that heparin assays underestimate drug levels in neonatal plasma unless the neonatal AT-III deficiency is fully corrected in the test system. The use of standard assays may lead to over-heparinization of newborn infants, thereby placing them at a higher risk of bleeding.
authors.affiliation: Department of Pediatrics, McMaster University Health Sciences Centre, Hamilton, Ontario, Canada.
authors.forename: B
authors.initials: B
authors.lastname: Schmidt
authors.forename: L
authors.initials: L
authors.lastname: Mitchell
authors.forename: F
authors.initials: F
authors.lastname: Ofosu
authors.forename: M
authors.initials: M
authors.lastname: Andrew
mesh_terms: D000990:Antithrombin III / Q000032:analysis; D005312:Fetal Blood / Q000032:analysis*; D006493:Heparin / Q000097:blood*; D006801:Humans; D007231:Infant, Newborn
chemical_list: D000990:Antithrombin III; D006493:Heparin