title: Severe Hemolysis and Pulmonary Hypertension in a Neonate With Upshaw-Schulman Syndrome.
abstract: Pulmonary involvement is extremely rare in thrombotic thrombocytopenic purpura. In this report, we present a girl patient with congenital thrombotic thrombocytopenic purpura, known as Upshaw-Schulman syndrome (USS), complicated with severe hemolysis and pulmonary hypertension (PH). The assay results of a disintegrin-like and metalloprotease with thrombospondin type 1 motifs 13 (ADAMTS13) activity measured by FRETS-VWF73 and ADAMTS13-act-ELISA were different. Hyperbilirubinemia (total bilirubin, 25.3 mg/dL) interfered strongly with the FRETS-VWF73 assay. Plasma levels of ADAMTS13 activity by act-ELISA were <0.5% of normal. The diagnosis of USS was confirmed by ADAMTS13 gene analysis, which showed compound heterozygous mutations of p.G139Vfs*17 and p.I673F. The p.G139Vfs*17 mutation was previously unreported, and its effect in splicing was confirmed by reverse transcription polymerase chain reaction. The patient received oxygen therapy for PH and exchange blood transfusion for severe hemolysis. The PH resolved without specific treatment. Based on these findings, the PH may have been caused by free hemoglobin that scavenged nitrogen oxide or platelet thrombi in the lungs caused by ADAMTS13 deficiency. Thus, severe PH can occur in neonatal patients with USS, and severe hemolysis might result in overestimation of ADAMTS 13 activity. Both possibilities are important for the diagnosis and management of USS.
authors.affiliation: Departments of Pediatrics, and.|Departments of Pediatric Cardiology, and.
authors.forename: Nobuyuki
authors.initials: N
authors.lastname: Tsujii
authors.affiliation: Departments of Pediatric Cardiology, and.
authors.forename: Isao
authors.initials: I
authors.lastname: Shiraishi
authors.affiliation: Molecular Pathogenesis, National Cerebral and Cardiovascular Center, Osaka, Japan.
authors.forename: Koichi
authors.initials: K
authors.lastname: Kokame
authors.affiliation: Departments of Pediatrics, and.
authors.forename: Midori
authors.initials: M
authors.lastname: Shima
authors.affiliation: Blood Transfusion Medicine, and.
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Fujimura
authors.affiliation: Division of Neonatal Intensive Care, Nara Medical University, Nara, Japan; and.
authors.forename: Yukihiro
authors.initials: Y
authors.lastname: Takahashi
authors.affiliation: Blood Transfusion Medicine, and mmatsumo@naramed-u.ac.jp.
authors.forename: Masanori
authors.initials: M
authors.lastname: Matsumoto
mesh_terms: D000071120:ADAMTS13 Protein / Q000235:genetics*; D004452:Echocardiography; D005260:Female; D006461:Hemolysis; D006801:Humans; D006976:Hypertension, Pulmonary / Q000209:etiology*; D007231:Infant, Newborn; D009154:Mutation; D011697:Purpura, Thrombotic Thrombocytopenic / Q000150:complications* / Q000151:congenital / Q000235:genetics
chemical_list: D000071120:ADAMTS13 Protein; C099604:ADAMTS13 protein, human