Introduction Paroxysmal nocturnal hemoglobinuria (PNH) is a rare, life-threatening hematologic disorder characterized by complement-mediated hemolysis, thrombosis, and bone marrow failure. Although complement inhibitors have transformed the prognosis of PNH, access to these therapies remains limited, particularly in low- and middle-income countries. Beyond hemolysis and thrombosis, PNH imposes a substantial burden on patients' quality of life (QoL), including persistent fatigue, pain, and sexual dysfunction—symptoms often underrecognized and undertreated.

Objective To compare QoL, fatigue, and sexual health in PNH patients with and without access to complement inhibitor therapy versus healthy controls.

Methods We conducted a cross-sectional study of adult PNH patients with treatment indications, including those receiving complement inhibitors, those without access to treatment, and healthy controls. Participants completed validated Spanish-language questionnaires: EQ-5D-5L (general health), EORTC QLQ-C30 (QoL), FACIT-F (fatigue), a PNH Symptom Questionnaire, and sex-specific sexual health scales—the Female Sexual Function Index (FSFI) for women and the International Index of Erectile Function (IIEF) for men. Group comparisons were performed using Wilcoxon, Fisher's exact test, Kruskal–Wallis test and Pearson correlations.

Results A total of 94 participants were included: 15 untreated PNH patients, 32 receiving complement inhibitor therapy, and 47 healthy controls.

The mean age was 42 years. Females comprised 40.0% of the untreated group and 65.6% of the treated group (p=0.236). Being married or in a partnership was more common among treated patients (53.1%) compared to untreated patients (26.7%) and controls (31.9%) (p=0.065). Physical activity was reported by 33.3% of untreated patients, 43.8% of treated patients, and 51.1% of controls (p=0.566).

Quality of life, assessed via EORTC QLQ-C30, differed significantly between PNH patients (treated and untreated) and controls across several domains: physical functioning (p<0.001), role functioning (p<0.001), emotional (p<0.02), social functioning (p<0.001), global health (p<0.001), fatigue (p<0.001), nausea/vomiting (p<0.001), and pain (p<0.001). Differences were also noted in dyspnea, insomnia, appetite loss, and financial difficulties (all p<0.001).

Post hoc comparisons between treated and untreated patients revealed significant differences only in dyspnea (p=0.006) and global health (p=0.037).

Fatigue, measured via the FACIT-F scale, was moderate in 26.7% of untreated patients vs. 3% of those treated. Standardized fatigue scores differed significantly across groups (p<0.001), with pairwise analysis confirming worse fatigue in untreated vs. treated patients (p=0.0457).

Six key PNH-related symptoms were assessed. Untreated patients had significantly higher fatigue scores (median 3.00, IQR 2.00–4.00) compared to treated patients (2.00, IQR 1.00–3.00) and controls (1.00, IQR 0.00–2.00) (p=0.0016). Dyspnea (p=0.001), pain (p=0.0003), abdominal pain (p=0.0003), and sleep disturbances (p=0.0052) were also more frequent in untreated patients.

General health status, assessed with EQ-5D-5L, showed no significant overall difference between treated and untreated patients (p=0.139), except in the anxiety/depression domain, which was worse in untreated individuals (p=0.0334). Both untreated (p=0.0001) and treated (p=0.0008) patients reported significantly lower general health scores compared to controls.

No significant differences were found in FSFI scores across groups. However, erectile dysfunction (per IIEF) was more prevalent in PNH patients—66.7% untreated, 54.5% treated—compared to 9.1% of controls (p=0.001), with a trend toward more severe dysfunction in the untreated group (p=0.056).

Conclusions PNH significantly impairs QoL, especially in patients lacking access to treatment. Fatigue, pain, and dyspnea were markedly worse in untreated individuals; however, even treated patients continued to report persistent symptoms and reduced QoL compared to healthy controls. These findings underscore that while complement inhibitors improve clinical outcomes, they may not fully restore well-being. Equitable access to therapy is essential—not only to prolong survival but also to enhance daily functioning and preserve dignity in patients with this rare disease. Incorporating patient-reported outcomes into routine care can help inform more holistic, patient-centered policies.

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2025
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