Global Epidemiology of Paroxysmal Nocturnal Hemoglobinuria: A Systematic Literature Review

BACKGROUND: Paroxysmal nocturnal hemoglobinuria (PNH) is a rare acquired hematological disorder characterized by chronic intravascular hemolysis and an increased risk of thrombosis. A systematic synthesis of disease epidemiology is essential to understand disease patterns, improve timely diagnosis, and guide healthcare policies. This review aims to consolidate contemporary estimates of PNH incidence and prevalence globally and describe any observed trends in these epidemiological parameters. METHODS: A systematic search of electronic databases was performed in November 2024 and identified 27 studies published between 2006 and 2024 following PRISMA guidelines. All population-based observational studies reporting incidence or prevalence measures of PNH were included, with no restrictions on age or geography; the synthesis of results focused on studies evaluated as medium or high-quality based on a structured assessment. RESULTS: The annual incidence of patients diagnosed with PNH ranged from 0.17 to 0.35 per 100,000 population between 2002 and 2022 in the majority of high-quality studies. Regional variability emerged: studies from countries with high healthcare system quality scores consistently reported higher incidence estimates than those from countries with low scores. Yearly prevalence estimates in 2010-2021 ranged from 1.1 to 2.1 per 100,000 population, while longer-period prevalence (10-17 years) ranged from 1.5 to 6.4 per 100,000 population. DISCUSSION: The prevalence of diagnosed PNH has been steadily growing since 2006 across all regions, possibly reflecting improved survival rates following the introduction of effective therapies or improved diagnostic practices. Despite disruptions observed during the COVID-19 pandemic (2020-2021), this upward trend is expected to continue as treatment access improves globally. The lower incidence reported in the regions with lower healthcare quality scores reflects potential underdiagnosis of PNH or unequal access to healthcare, highlighting the need for strengthening healthcare systems to ensure timely diagnosis and access to treatment of PNH. CONCLUSIONS: This review provides updated global estimates of the incidence and prevalence of PNH, offers new insights into epidemiological trends, and highlights potential regional inequities in diagnosis and treatment. The results aim to support future research initiatives and inform healthcare strategies to improve outcomes for patients with PNH.