Unmasking PNH: Epidemiological and clinical insights from Qatar

Abstract

Abstract background Paroxysmal nocturnal hemoglobinuria (PNH) is a rare, acquired clonal stem cell disorder caused by somatic mutations in the PIGA gene. Its clinical presentation is heterogeneous, ranging from intravascular hemolysis to bone marrow failure, overlapping with aplastic anemia and myelodysplastic syndromes (MDS), and a high risk of thrombosis. Data on the epidemiology and clinical characteristics of PNH in Qatar remain limited. Our study aims to shed light on this orphan disease assessing incidence and the clinical characteristics in Qatar. Methods We retrospectively reviewed patients with identified PNH clones with deficient levels of glycosylphosphaditdyinositol linked antigens and anchor proteins on red cells, monocytes and granulocytes using high-sensitivity flow cytometry with GPI-linked antibodies (CD59, CD14, CD24 and fluorescent aerolysin (FLAER)). The study was conducted at the National Center for Cancer Care and Research (NCCCR)at HMC over nearly a decade (01 January 2015 – 30 April 2025). Demographic, clinical, hematologic, and flow cytometric data were collected and analyzed using descriptive statistics. Results A total of 63 patients with PNH clones were identified among 1005 sample sent for PNH testing during the study period, with a median age of 36 years (16–66) and a male predominance (78%). For the study period of 10.30 years, this corresponds to an incidence rate of 2.28 cases per million per year (based on the Qatar population of 2.235 million on 31 December 2014 and 3.098 million on 30 April 2024). This rate is generally consistent with worldwide estimates. The main indications for referral were pancytopenia (80%), anemia (10%), and thrombosis (5%).The patients were classified based on granulocyte clone size into 4 groups: Minor clone( <1%) in 34% of cases, small clones (1–10%) in 35%, intermediate clones (10–50%) in 12%, and large clones (>50%) in 19%. Among patients with large clones, 67% presented with classical hemolytic PNH and 33% with aplastic PNH (aplastic anemia or hypoplastic MDS). Two cases of classical hemolytic PNH presented with thrombosis at unusual sites. Conclusions This study represents the first comprehensive investigation of PNH in Qatar, encompassing a large cohort of screened patients. The findings reveal a notably high detection rate, underscoring increased clinical awareness and the growing recognition of PNH as a relevant differential diagnosis, particularly in patients presenting with pancytopenia or bone marrow failure syndromes. High-sensitivity flow cytometry is pivotal in detecting small yet clinically significant PNH clones, which may otherwise go unnoticed. These insights not only enhance local diagnostic practices but also contribute valuable regional data to the global understanding of this rare hematologic disorder.