Anemia and Patient-Reported Outcomes in Patients With Paroxysmal Nocturnal Hemoglobinuria: A Real-World Observational Study.

INTRODUCTION: Paroxysmal nocturnal hemoglobinuria (PNH) is a rare hematologic disorder characterized by complement-mediated hemolysis, thrombosis, bone marrow failure, and anemia. Although current treatments improve outcomes, patients still experience hemolysis and could remain anemic with a negative impact on quality of life (QoL). The aim of this study was to assess whether patient-reported outcomes (PROs) distinguish PNH patients with/without hemolysis and evaluate factors associated with PROs. METHODS: In this international, multicenter, observational study, 97 PNH patients witfrom Italy and the UK completed the EORTC QLQ-C30 and QLQ-AA/PNH measures at baseline and after 2 weeks. Clinical, biochemical, and treatment data were collected. Hemolysis was defined as LDH ≥ 1.5 × upper normal limit. PRO scores were compared between patients above and below this threshold. Associations of PROs with patient and disease factors were analyzed. RESULTS: Of 97 patients (mean age 49 ± 15), 24.7% were anemic (Hb < 10 g/dL) and 16% had hemolysis. QoL did not differ significantly by hemolysis status. However, anemia was associated with significantly lower EORTC QLQ-C30 global health and functional scores (p < 0.05), particularly in physical, role, and social domains, and with worse QLQ-AA/PNH emotional, cognitive, and physical functioning, as well as greater illness intrusiveness and stigmatization. Fatigue, dyspnea, and pain were common symptoms in anemic patients. QLQ-AA/PNH scores showed high internal consistency (Cronbach's α > 0.7) and test-retest reliability (ICC: 0.72-0.95). CONCLUSIONS: Anemia, but not residual hemolysis, was associated with impaired QoL across multiple domains. Addressing anemia alongside hemolysis may improve PROs in the management of PNH. TRIAL REGISTRATION: The authors have confirmed clinical trial registration is not needed for this submission.