title: Paroxysmal nocturnal hemoglobinuria clone in 103 Brazilian patients: diagnosis and classification.
abstract: BACKGROUND
  Paroxysmal nocturnal hemoglobinuria is an acquired chronic hemolytic anemia, which often manifests as peripheral blood cytopenias and thrombosis.
  
  
  OBJECTIVE
  The aim of this study is to describe a Brazilian population of paroxysmal nocturnal hemoglobinuria patients.
  
  
  METHODS
  One hundred and three paroxysmal nocturnal hemoglobinuria cases were retrospectively reviewed and the clinical presentation, thrombosis, survival, and clone size were assessed. Diagnosis was established by flow cytometry.
  
  
  RESULTS
  Fifty-two male and 51 female patients with a median age of 24.1 years (5.5-62 years) were studied. Clinical symptoms included hemoglobinuria (18.4%), infection (46.6%) and thrombosis (16.5%), and 80.6% had pancytopenia. Patients were classified as classic paroxysmal nocturnal hemoglobinuria (10), paroxysmal nocturnal hemoglobinuria with aplastic anemia (39), and paroxysmal nocturnal hemoglobinuria with subclinical features and aplastic anemia (54). There were significant differences in terms of median age, size of clone, clinical symptoms, and peripheral blood cell counts between the three subcategories. The clone size in erythrocytes and granulocytes were respectively 0.04% (range: 0-18%) and 7.3% (range: 0.3-68.7%) in patients with subclinical features and aplastic anemia, 15.8% (range: 0-99.7%) and 63.0% (range: 1.7-99.8%) in patients with aplastic anemia alone, and 82.2% (range: 0-99.85%) and 98.0% (81.3-100.0%) in Classic disease. Statistical differences were identified for platelets (p-value=0.001), lactate dehydrogenase (p-value=0.002) and the clone size (p-value<0.001) in patients who suffered thrombotic events compared to those who did not. Overall survival was 81.7%, with patients with subclinical features and aplastic anemia having lower overall survival (76.5%).
  
  
  CONCLUSIONS
  This retrospective review of 103 patients over an 11-year period represents the largest collection of paroxysmal nocturnal hemoglobinuria cases from a single center in Brazil. Flow cytometry showed that a larger clone was associated with classical symptoms and increased risk of thrombosis, even in patients with bone marrow failure, whereas a smaller clone was associated with bone marrow aplasia.
authors.affiliation: Universidade Federal do Paraná (UFPR), Curitiba, PR, Brazil. Electronic address: apazamb@gmail.com.
authors.forename: Ana Paula
authors.initials: AP
authors.lastname: de Azambuja
authors.affiliation: Universidade Federal do Paraná (UFPR), Curitiba, PR, Brazil.
authors.forename: Mariester
authors.initials: M
authors.lastname: Malvezzi
authors.affiliation: Universidade Federal do Paraná (UFPR), Curitiba, PR, Brazil.
authors.forename: Marco Antonio
authors.initials: MA
authors.lastname: Bitencourt
authors.affiliation: Universidade Federal do Paraná (UFPR), Curitiba, PR, Brazil.
authors.forename: Michel Michels
authors.initials: MM
authors.lastname: Oliveira
authors.affiliation: Universidade Federal do Paraná (UFPR), Curitiba, PR, Brazil.
authors.forename: Larissa Alessandra
authors.initials: LA
authors.lastname: Medeiros
authors.affiliation: Universidade Federal do Paraná (UFPR), Curitiba, PR, Brazil.
authors.forename: Ricardo
authors.initials: R
authors.lastname: Pasquini
keywords: Bone marrow diseases; Flow cytometry; Hemoglobinuria; Paroxysmal
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