Paroxysmal nocturnal hemoglobinuria (PNH) imposes a substantial and often underrecognized burden on patient quality of life (QOL), driven by symptoms such as chronic fatigue, anemia, and pain, as well as the unpredictability of breakthrough hemolysis and thrombosis. Even in the era of complement inhibition, many patients continue to experience symptoms that affect daily functioning, productivity, and emotional well-being.

PNH is a rare acquired clonal disorder that can lead to intravascular hemolysis, an increased risk of thrombosis, and, in some patients, bone marrow failure. Without treatment, PNH can have a high mortality rate and can lead to numerous symptoms.

The symptoms and complications that patients with PNH can present with are often nonspecific. They include thrombosis, anemia, fatigue, pain, headaches, and spasms resulting in difficulty swallowing and erectile dysfunction. Patients with PNH can also present with unusual thromboses, including arterial and venous. These thromboses can have a significant impact on the patient and their QOL, especially if they are having recurrent thromboses without a clear underlying etiology. Additionally, when patients with PNH have hemolytic anemia, they can experience shortness of breath, fatigue, dizziness, and lightheadedness, and they might even need blood transfusions. This can be quite burdensome. Other patients may present with symptoms related to smooth muscle contractions due to nitric oxide scavenging, such as painful esophageal spasms, headaches, vague abdominal pain, and erectile dysfunction.

Patients with PNH can really suffer from the variety of presentations. In terms of which symptoms impact their QOL, it really depends on how they present. If they are presenting with severe anemia, those symptoms are often greatly impacting their QOL. If they are presenting with pain, that can be very debilitating. If they are presenting with thrombosis requiring intervention or long-term anticoagulation, that can also have a big impact.

PNH can have an especially significant impact on QOL if the patient is undiagnosed and untreated. Because PNH is relatively rare, some patients may have a lengthy delay between when they first start having symptoms and when they start treatment. Patients who suffered from undiagnosed PNH for a while will often say that they feel better once they are on therapy. However, if you ask any patient with or without PNH in my clinic whether they are tired, the majority will say yes. But is their fatigue related to their PNH? That can be a challenging distinction to make. In my experience, once patients with PNH are on a stable therapy, younger individuals without other medical problems tend to function fairly well in their daily lives.

Patients often have PNH-related anxiety. This may be related to concerns about breakthrough hemolysis or contracting an illness that could exacerbate their PNH. Moreover, assessing cognition can be challenging in patients with PNH, especially in older individuals. These patients often have other medical problems, and we have to wonder if any identified cognitive dysfunction is related to their PNH or another condition. We currently do not have easy standardized ways to assess cognition in the clinic. We need more data and more research in this area because, as our therapies improve, patients with PNH are growing older with us and life expectancy is now closer to normal.

The big challenge now is understanding what parts of PNH management impact QOL. Some patients say that taking a pill 2 or 3 times a day is too much and stresses them out. Others find coming to an infusion center every 8 weeks to be tiring. So, we have to ask patients what they want. When choosing therapy together, we have to take into consideration factors such as clinical efficacy, adverse effects, flexibility, lifestyle choices, access, and cost. We have improved our patients’ lives in so many ways. Now our goals should not just be reducing mortality and morbidity but also determining how to improve their QOL.