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 presenta tion 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 suc cessfully, 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 na tive 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.

Keywords

Antithrombin Budapest 3 deficiency Neonatal thrombosis Molecular diagnosis Antithrombin concentrate Heparin resistance.

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