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.

Early indicators of neonatal‐onset hereditary thrombotic thrombocytopenia purpura

“…Severe jaundice can occur soon after birth in newborns with either hTTP or ABO incompatibility, 1 , 2 , 15 but here we found earlier‐onset jaundice in newborns with hTTP, all within 24 h, than in newborns with ABO incompatibility. Consistent with these findings, Tsujii et al . 16 reported a case of hTTP with jaundice at 6 h after birth, and Tanabe et al .…”

Morbidities and mortality in patients with hereditary thrombotic thrombocytopenic purpura

“…Prophylactic treatment was reported for 110 (53%) of the 207 symptomatic patients who survived infancy. Prophylaxis began at a median age of 14 years (range, newborn 21 -70 23 years). Prophylaxis was almost always with plasma, commonly described as 1 to 3 units of plasma at 2- to 3-week intervals.…”

“…Only 3 infants were suspected to have hTTP, appropriately treated and survived. 21,22 The diagnosis of hTTP should be considered in all newborn infants who have severe hyperbilirubinemia. Although documentation of ADAMTS13 deficiency may require several days, empirical plasma infusion is a simple, life-saving treatment.…”

“…In 3 of the 74 surviving infants, hTTP was promptly suspected, effectively treated and subsequently confirmed. 21,22 Among the remaining 71 infants, 37 were treated with empirical whole blood exchange transfusion. hTTP was diagnosed in these 71 patients at ages 1 month-21 years (median age, 5 years).…”

A novel homozygous frameshift mutation in Exon 7 of the ADAMTS13 gene in a patient with congenital thrombotic thrombocytopenic purpura from India: a case report

“…Most reported mutations are missense. Interestingly, only five frameshift insertion mutations have been reported so far: p.W28LfsX111, p.R125VfsX6, a p.G139VfsX17 insertion mutation found in the metalloprotease region of the gene, and p.L1258VfsX36 and p.E1382RfsX6 found in the complement components C1r/C1s, Uegf [sea urchin fibropellins], and Bone morphogenic protein 1 (CUB‐1) and CUB‐2 regions, respectively . Some studies have also reported recurrent mutations in TTP; for instance, p.E1382RfsX6 (c.4143_4144dupA) in central Norway .…”