title: Rapid genetic diagnosis in neonatal pulmonary artery thrombosis caused by homozygous antithrombin Budapest 3.
abstract: We report a case of spontaneous left pulmonary artery thrombosis in a 3-day-old male neonate. The presentation of heparin resistance and thrombosis raised the possibility of a type II heparin binding site antithrombin deficiency. A continuous infusion of antithrombin concentrate was used successfully, following failure of plasma, to correct the heparin resistance. Rapid genetic analysis allowed sequencing of the antithrombin gene within 5 working days. This showed the infant to be homozygous for the substitution of C to T at nucleotide 2759. This base change causes mutation of the native leucine at codon 99 to a phenylalanine. This antithrombin variant has been previously reported (antithrombin Budapest 3) and results in reduced binding of heparin to antithrombin. Such a molecular diagnostic approach is feasible and warranted in such cases of neonatal thrombosis because of the diagnostic difficulties encountered.
authors.affiliation: Haemophilia Reference Centre, St.Thomas' Hospital, London, UK.
authors.forename: S A
authors.initials: SA
authors.lastname: Brown
authors.forename: M
authors.initials: M
authors.lastname: Mitchell
authors.forename: J A
authors.initials: JA
authors.lastname: Cutler
authors.forename: G
authors.initials: G
authors.lastname: Moore
authors.forename: M P
authors.initials: MP
authors.lastname: Smith
authors.forename: G F
authors.initials: GF
authors.lastname: Savidge
mesh_terms: D020152:Antithrombin III Deficiency / Q000235:genetics*; D001483:Base Sequence; D016913:Blood Component Transfusion; D003596:Cytosine; D005260:Female; D006493:Heparin / Q000627:therapeutic use; D006720:Homozygote; D006801:Humans; D007231:Infant, Newborn; D008297:Male; D010290:Parents; D010314:Partial Thromboplastin Time; D017354:Point Mutation; D011655:Pulmonary Embolism / Q000175:diagnosis* / Q000235:genetics* / Q000628:therapy; D013941:Thymine
chemical_list: D003596:Cytosine; D006493:Heparin; D013941:Thymine