Pilot dose-finding and safety study of bivalirudin in infants <6 months of age with thrombosis.
BACKGROUND
Thrombosis is not uncommon in children with serious medical conditions. Unfractionated heparin, the most commonly used anticoagulant in the acute management of thrombosis, has significant pharmacologic limitations, especially in infants. Newer anticoagulants have improved properties relative to heparin, and this may enhance the outcome in children.


OBJECTIVE
To determine dosing, and to assess the safety and efficacy of bivairudin for infants with thrombosis.


METHODS
Infants <6 months old were chosen for this pilot study as they may most benefit from a direct thrombin inhibitor because of their physiologically low antithrombin levels. This was an open label, dose-finding and safety study. Patients received one of three bolus doses and one of two initial infusion doses with subsequent dosing adjusted utilizing the activated partial thromboplastin time. Safety was assessed by specific bleeding endpoints. Efficacy was determined by reassessing the initial imaging study at 48-72 h and by measurement of molecular markers of thrombin generation.


RESULTS
Sixteen patients completed the study. All three bolus doses resulted in therapeutic anticoagulation, as did both initial infusion doses. A dose-response effect was noted for the continuous infusion but not the bolus dosing. Two patients met the study criteria for major bleeding, both with gross hematuria, which resolved with a reduction in the bivalirudin infusion rate. In terms of efficacy, 37.5% of patients had complete or partial resolution of their thrombosis by 48-72 h. There was a significant decrease in all three molecular markers of thrombin generation.


CONCLUSIONS
This study demonstrates the potential utility of bivalirudin in the pediatric population.
Children's Hospital of Orange County, Los Angeles, CA, USA. gyoung@chla.usc.edu
G
G
Young
M D
MD
Tarantino
J
J
Wohrley
L C
LC
Weber
M
M
Belvedere
D J
DJ
Nugent
D000925:Anticoagulants / Q000008:administration & dosage*; D005260:Female; D006629:Hirudins / Q000008:administration & dosage*; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008297:Male; D010314:Partial Thromboplastin Time; D010446:Peptide Fragments / Q000008:administration & dosage*; D010865:Pilot Projects; D011446:Prospective Studies; D011994:Recombinant Proteins / Q000008:administration & dosage; D013927:Thrombosis / Q000188:drug therapy*; D016896:Treatment Outcome
D000925:Anticoagulants; D006629:Hirudins; D010446:Peptide Fragments; D011994:Recombinant Proteins; C074619:bivalirudin