Different clinical characteristics of paroxysmal nocturnal hemoglobinuria in pediatric and adult patients.

Studies of children with paroxysmal nocturnal hemo-globinuria (PNH) are scarce and include limited numbers of patients. We compared demographic and clinical characteristics of children and adults in the International PNH Registry. Our data show that, compared to adults with PNH, children had smaller PNH clones with more frequent severe cytopenia or previous marrow aplasia. In contrast, hemolysis was present in similar proportions, and both children and adults suffered from major adverse vascular events (MAVE), such as thrombotic events (TE), which seemed more prominent in adults. PNH is an acquired clonal hematopoietic stem cell disorder characterized by complement-mediated hemolysis, thrombosis, and bone marrow failure. 1-3 It is a very rare disease with a worldwide incidence estimated at 1.3 cases per million population. 4 The onset of PNH is typically in adulthood, with pediatric cases accounting for only 5-10% of reported cases; 1,5 studies of children with PNH have, therefore, been limited to case reports and small series. 5-7 The largest PNH pediatric series included 26 patients and was published in 1991, when flow cytometry was not yet routinely available. The International PNH Registry is the largest PNH data repository to date, and contains a wide range of laboratory , clinical, and patient-reported information. 8 The Registry is overseen by an independent committee of international medical PNH experts. Patients with detectable glycosylphosphatidylinositol (GPI)-deficient granulocytes or a " granulocyte PNH clone " (≥0.01%) are eligible for inclusion in the Registry, regardless of disease severity, comorbidities, or treatments. This retrospective analysis included patients enrolled in or before June 2015. Because the objective of this analysis was to study the natural presentation of PNH, patients being treated with eculizumab at the time of enrollment were excluded. Children were <18 years of age at the time of disease start and time of enrollment, while adults were ≥18 years of age at disease start and enrollment. Patients who were <18 years at disease start but over 18 years at enrollment were excluded. The degree of cytopenia was classified using the following criteria: 9,10 none (neutrophils ≥1.5x10 9 /L and platelets ≥100x10 9 /L), moderate (neutrophils <1.5x10 9 /L or platelets <100x10 9 /L), or severe (neutrophils <0.5x10 9 /L or platelets <20x10 9 /L). Hemolytic activity was defined as serum lactate dehydrogenase ≥1.5x the upper limit of normal and/or reticulocytes ≥60x10 9 /L. Duration of disease was the time between disease start and enrollment into the Registry. …