title: Pediatric catheterization laboratory anticoagulation with bivalirudin.
abstract: BACKGROUND
  Pediatric physicians regularly face the problem of uncertain procedural anticoagulation in children, especially in neonates. We sought to evaluate the safety, plasma concentration (pharmacokinetics, PK), pharmacodynamics (PD), and dosing guidelines of bivalirudin when used as a procedural anticoagulant in pediatric percutaneous intravascular procedures.
  
  
  RESULTS
  Pediatric subjects undergoing percutaneous intravascular procedures for congenital heart disease were enrolled and received the current weight-based dose used in percutaneous coronary interventions (0.75 mg/kg bolus, 1.75 mg/kg/hr infusion). Blood samples for PK/PD analyses were drawn, and safety was evaluated by monitoring bleeding and thrombosis events. A total of 110 patients (11 neonates, 33 infants, 32 young children, and 34 older children) were enrolled; 106 patients received the protocol dose. The PK/PD response of bivalirudin was predictable and behaved in a manner similar to that in adults. Weight-normalized bivalirudin clearance rates were more rapid in neonates and decreased with increasing age. Bivalirudin concentrations were slightly lower in neonates, with a trend to an increase with age. Activating clotting time response was consistent with adult studies and prolonged in all age groups, and there was reasonable correlation between activating clotting time and bivalirudin plasma concentrations across all age groups. There were few major bleeding (2 of 110, 1.8%) or thrombotic events (9 of 110, 8.2%) reported.
  
  
  CONCLUSIONS
  PK/PD response of bivalirudin in the pediatric population is predictable and behaves in a manner similar to that in adults. Using adult dosing, bivalirudin safely provided the expected anticoagulant effect in the pediatric population undergoing intravascular procedures for congenital heart disease.
authors: Division of Cardiology, Children's Hospital of Michigan, Detroit, Michigan, USA. tforbes@dmc.org
authors: Thomas J
authors: TJ
authors: Forbes
authors: Ziyad M
authors: ZM
authors: Hijazi
authors: Guy
authors: G
authors: Young
authors: Jeremy M
authors: JM
authors: Ringewald
authors: Paolo M
authors: PM
authors: Aquino
authors: Robert N
authors: RN
authors: Vincent
authors: Athar M
authors: AM
authors: Qureshi
authors: Jonathan J
authors: JJ
authors: Rome
authors: John F
authors: JF
authors: Rhodes
authors: Thomas K
authors: TK
authors: Jones
authors: William B
authors: WB
authors: Moskowitz
authors: Ralf J
authors: RJ
authors: Holzer
authors: Rolando
authors: R
authors: Zamora
mesh_terms: D000293:Adolescent; D000367:Age Factors; D000925:Anticoagulants / Q000008:administration & dosage* / Q000009:adverse effects / Q000097:blood / Q000493:pharmacokinetics; D006328:Cardiac Catheterization; D002648:Child; D002675:Child, Preschool; D005260:Female; D006330:Heart Defects, Congenital / Q000097:blood / Q000175:diagnosis / Q000628:therapy; D006470:Hemorrhage / Q000139:chemically induced; D006629:Hirudins / Q000008:administration & dosage* / Q000009:adverse effects / Q000097:blood / Q000493:pharmacokinetics; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008297:Male; D010446:Peptide Fragments / Q000008:administration & dosage* / Q000009:adverse effects / Q000097:blood / Q000493:pharmacokinetics; D011446:Prospective Studies; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000009:adverse effects / Q000097:blood / Q000493:pharmacokinetics; D018570:Risk Assessment; D012307:Risk Factors; D013927:Thrombosis / Q000097:blood / Q000209:etiology / Q000517:prevention & control*; D016896:Treatment Outcome; D014481:United States
chemical_list: D000925:Anticoagulants; D006629:Hirudins; D010446:Peptide Fragments; D011994:Recombinant Proteins; C074619:bivalirudin