title: A Pilot Study of Antithrombin Replacement Prior to Cardiopulmonary Bypass in Neonates.
abstract: Neonates have low levels of antithrombin. Inadequate anticoagulation during cardiopulmonary bypass (CPB) due to low antithrombin activity may result in a poor preservation of the coagulation system during bypass. We hypothesize that antithrombin replacement to neonates prior to CPB will preserve the hemostatic system and result in less postoperative bleeding. A randomized, double-blinded, placebo-controlled pilot study of antithrombin replacement to neonates prior to CPB was conducted. Preoperative antithrombin levels determined the dose of recombinant antithrombin or placebo to be given. Antithrombin levels were measured following the dosing of the antithrombin/placebo, after initiation of bypass, near the completion of bypass, and upon intensive care unit admission. Eight subjects were enrolled. No subject had safety concerns. Mediastinal exploration occurred in two antithrombin subjects and one placebo subject. Antithrombin activity levels were significantly higher in the treated group following drug administration; levels continued to be higher than preoperatively but not different from the placebo group at all other time points. Total heparin administration was less in the antithrombin group; measurements of blood loss were similar in both groups. A single dose of recombinant antithrombin did not maintain 100% activity levels throughout the entire operation. Although no safety concerns were identified in this pilot study, a larger trial is necessary to determine clinical efficacy.
authors.affiliation: Section of Critical Care, Medical College of Wisconsin, Milwaukee, WI, USA.|Herma Heart Center at Children's Hospital of Wisconsin, Milwaukee, WI, USA.
authors.forename: Robert A
authors.initials: RA
authors.lastname: Niebler
authors.affiliation: Section of Critical Care, Medical College of Wisconsin, Milwaukee, WI, USA.
authors.forename: Katherine J
authors.initials: KJ
authors.lastname: Woods
authors.affiliation: Section of Critical Care, Medical College of Wisconsin, Milwaukee, WI, USA.
authors.forename: Kathleen
authors.initials: K
authors.lastname: Murkowski
authors.affiliation: Section of Critical Care, Medical College of Wisconsin, Milwaukee, WI, USA.|Herma Heart Center at Children's Hospital of Wisconsin, Milwaukee, WI, USA.
authors.forename: Nancy S
authors.initials: NS
authors.lastname: Ghanayem
authors.affiliation: Department of Anesthesiology, Medical College of Wisconsin, Milwaukee, WI, USA.|Herma Heart Center at Children's Hospital of Wisconsin, Milwaukee, WI, USA.
authors.forename: George
authors.initials: G
authors.lastname: Hoffman
authors.affiliation: Department of Cardiothoracic Surgery, Medical College of Wisconsin, Milwaukee, WI, USA.|Herma Heart Center at Children's Hospital of Wisconsin, Milwaukee, WI, USA.
authors.forename: Michael E
authors.initials: ME
authors.lastname: Mitchell
authors.affiliation: Section of Hematology, Medical College of Wisconsin, Milwaukee, WI, USA.
authors.forename: Rowena C
authors.initials: RC
authors.lastname: Punzalan
authors.affiliation: Section of Hematology, Medical College of Wisconsin, Milwaukee, WI, USA.
authors.forename: J Paul
authors.initials: JP
authors.lastname: Scott
authors.affiliation: Section of Quantitative Health Sciences, Department of Pediatrics, Medical College of Wisconsin, Milwaukee, WI, USA.
authors.forename: Pippa
authors.initials: P
authors.lastname: Simpson
authors.affiliation: Department of Cardiothoracic Surgery, Medical College of Wisconsin, Milwaukee, WI, USA.|Herma Heart Center at Children's Hospital of Wisconsin, Milwaukee, WI, USA.
authors.forename: James S
authors.initials: JS
authors.lastname: Tweddell
mesh_terms: D000925:Anticoagulants / Q000008:administration & dosage* / Q000009:adverse effects / Q000097:blood; D000990:Antithrombin III / Q000008:administration & dosage* / Q000009:adverse effects; D001777:Blood Coagulation / Q000187:drug effects*; D001780:Blood Coagulation Tests; D002315:Cardiopulmonary Bypass / Q000009:adverse effects; D004311:Double-Blind Method; D005240:Feasibility Studies; D006330:Heart Defects, Congenital / Q000097:blood / Q000175:diagnosis / Q000601:surgery*; D006493:Heparin / Q000008:administration & dosage; D006801:Humans; D007231:Infant, Newborn; D010865:Pilot Projects; D019106:Postoperative Hemorrhage / Q000097:blood / Q000209:etiology / Q000517:prevention & control*; D011994:Recombinant Proteins / Q000008:administration & dosage; D013997:Time Factors; D016896:Treatment Outcome; D014922:Wisconsin
chemical_list: D000925:Anticoagulants; D011994:Recombinant Proteins; D000990:Antithrombin III; D006493:Heparin
keywords: Blood; Cardiopulmonary bypass; Coagulation/Anticoagulation; Congenital heart disease; Pediatrics