Paroxysmal Nocturnal Hemoglobinuria – long lasting observations. Clinical characteristic and analysis of the size of the clone with glycosylphosphatidylinositol (GPI) anchor defect

Abstract

We present the analysis of 105 paroxysmal nocturnal hemoglobinuria (PNH) cases diagnosed in the period 1995-June 2011. PNH diagnosis was based on the analysis of the major clinical symptoms and on protein expression associated with glycosylphosphatidylinositol (GPI) anchor on erythrocytes and granulocytes assessed with flow fluorocytometry (FC). The analysis included patients with clone size 1% or bigger. The main clinical symptoms were: intravascular hemolysis (88.6%), hemoglobinuria (38.6%), thrombocytopenia (41.4%), bone marrow aplasia/ hypoplasia (45.7%), thromboses (20.0%). PNH clone size ranged from several percent to 99%; it was higher among granulocytes than among erythrocytes. Patients were divided into two groups: classic PNH and PNH with bone marrow failure. In both groups hemolysis was observed in approximately 90% of patients, hemoglobinuria in about 50% of patients with classic PNH and in 25% of patients with bone marrow failure; thrombocytopenia was observed in approximately 90% of patients with bone marrow failure and rarely in classic PNH; thrombotic events were found in 20% of both groups of patients. In classic PNH the median size of clone with defect in PNH erythrocytes and granulocytes was significantly higher than in PNH with bone marrow failure. Clone size with GPI defect on granulocytes in the classic PNH was always >20%, and <20% in a significant number of patients with bone marrow failure. In 8 such patients, subsequent studies revealed increase in the percentage of cells with defect. Follow up investigation of the size of the PNH clone seem therefore warranted.