Paroxysmal nocturnal hemoglobinuria clone in 103 Brazilian patients: diagnosis and classification

Abstract

BackgroundParoxysmal nocturnal hemoglobinuria is an acquired chronic hemolytic anemia, which often manifests as peripheral blood cytopenias and thrombosis.ObjectiveThe aim of this study is to describe a Brazilian population of paroxysmal nocturnal hemoglobinuria patients.MethodsOne 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.ResultsFifty-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%).ConclusionThis 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.

Clinical presentation, laboratory parameters, classification and flow cytometric analysis of patients of paroxysmal nocturnal haemoglobinuria in Pakistan

“…These findings are in accordance with haemoglobin of 7.4g/dl reported by Wang et al 17 However, Schrezenmeier et al 15 have reported higher haemoglobin levels. As compared in Table 4, De Azambuja et al 14 have reported low platelet counts as compared to our study. The reticulocyte percentage of our patients is comparable with that reported by Wang et al 17 We classified our patients into 3 subgroups.…”

“…These findings are consistent with those (5.6%) reported by Nishimura et al 16 in the Japanese population. However, much higher frequencies of 16.5% and 16.7% have been reported by De Azambuja et al 14 and Wang et al, 17 respectively. Our patients had median haemoglobin of 7.8g/dl at the time of presentation.…”

“…A.P. De Azambuja et al 14 have reported the age of the Brazilian patients as 24.1years. However, a much higher age, 42years, has been reported by Schrezenmeier et al 15 in the Western population.…”

“…The most common presenting clinical findings have been compared in Figure 1 with study conducted by A P De Azambuja et al 14 in the Brazilian population. In our study population, 6.9% patients presented with thrombosis.…”

Clinicopathological Profile of Paroxysmal Nocturnal Hemoglobinuria among Omani Patients: A Case Series

“…This has been observed in other series supporting the heterogeneity in the clinical phenotype of these patients. 20 In this cohort, one patient had a large PNH clone and an aggressive disease with hemolytic anemia and thrombosis involving portal, splenic, and superior mesenchymal veins. Previous data showed that the risk of thrombosis is greatest where PNH clones manifest > 50% in the neutrophils.…”