In real-world study, anemia tied to poorer quality of life for those with PNH
Shortage of healthy red blood cells may be worse than ongoing destruction
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Anemia, or a shortage of healthy red blood cells, may have a greater impact on quality of life than ongoing red blood cell destruction — the hallmark of paroxysmal nocturnal hemoglobinuria (PNH) — despite treatment in people with the rare acquired disease, a real-world study suggests.
Individuals with significant anemia — which in PNH can develop as red blood cells are destroyed in a process known as hemolysis — reported poorer overall health and greater difficulties with physical, emotional, cognitive, and social functioning, the data showed. Overall, “anemia was associated with significantly lower … global health,” according to the researchers.
In contrast, patient-reported outcomes did not differ significantly between those with and without residual hemolysis, defined as red blood cell destruction that persists despite treatment, specifically the use of complement inhibitor therapies, according to the researchers.
“Anemia, but not residual hemolysis, was associated with impaired [quality of life] across multiple domains,” the researchers wrote, adding that “addressing anemia alongside hemolysis may improve [patient-reported outcomes] in the management of PNH.”
The study, “Anemia and Patient-Reported Outcomes in Patients With Paroxysmal Nocturnal Hemoglobinuria: A Real-World Observational Study,” was published in the journal eJHaem by researchers in Europe.
PNH is a blood disorder in which red blood cells become vulnerable to attack by the complement system, a part of the immune system, causing them to break apart. This process, called hemolysis, can lead to anemia and other PNH symptoms, such as fatigue and shortness of breath. PNH can also cause serious complications, including bone marrow failure.
Complement inhibitors have transformed PNH treatment by blocking complement-driven hemolysis. However, some patients remain anemic despite treatment due to ongoing red blood cell destruction within blood vessels — known as intravascular hemolysis — or elsewhere in the body, when it’s called extravascular hemolysis. Anemia can also occur because the bone marrow fails to produce enough blood cells.
Persistent anemia can negatively affect a patient’s quality of life, the researchers noted.
Investigating quality of life in people with PNH
Although patient-reported outcomes are increasingly used to assess how PNH affects life quality, commonly used questionnaires may not fully capture PNH-specific outcomes, according to the scientists. Moreover, how residual hemolysis relates to patients’ reported quality of life and symptoms remains unclear, the team noted.
Now, researchers from Italy and the U.K. sought to determine whether patient-reported outcomes could distinguish people with PNH who had residual hemolysis from those who did not. The team also sought to identify other factors associated with these outcomes.
To that end, an observational study was launched at 12 centers in Italy and one in the U.K. between May 2021 and March 2024. Overall, the study involved 97 adults with a mean age of 49. Nearly all (98%) were receiving complement inhibitors, including investigational therapies.
A total of 24 patients (25%) had significant anemia, defined as hemoglobin levels below 10 grams per deciliter (g/dL), while 16 (16%) had residual intravascular hemolysis, defined as LDH levels at least 1.5 times the upper limit of normal. LDH is an enzyme commonly used as a marker of red blood cell destruction. Hemoglobin is an iron-rich protein inside red blood cells that carries oxygen from the lungs to the rest of the body.
Importantly, anemia and residual intravascular hemolysis do not always occur together in PNH. Patients can be anemic without intravascular hemolysis due to other factors, such as red blood cell destruction in the spleen and liver (extravascular hemolysis) or bone marrow failure. Likewise, patients can have mild ongoing intravascular hemolysis without their hemoglobin dropping low enough to cause significant anemia.
Anemia tied to poorer health, physical functioning in PNH
Patient-reported outcomes were assessed using two questionnaires: the EORTC QLQ-C30 and the QLQ-AA/PNH. The 30-question EORTC QLQ-C30 assesses nine functional domains, overall health, and symptoms. Scores range from zero to 100, with higher functional scores indicating better functioning and higher symptom scores implying more severe symptoms. The longer QLQ-AA/PNH, with 54 questions, covers 12 areas of functioning and symptoms relevant to PNH. Scores also range from 0 to 100, with higher scores reflecting a better quality of life.
Scores on the EORTC QLQ-C30 indicated that people with PNH have a relatively preserved overall quality of life compared with the general population, according to the researchers.
Additionally, neither EORTC QLQ-C30 nor QLQ-AA/PNH scores differed significantly between people with and without residual hemolysis. The researchers cautioned, however, that the small number of patients with residual hemolysis limited the study’s ability to detect potential differences in quality of life.
Anemia showed a different pattern, though, the researchers noted. On the EORTC QLQ-C30, higher hemoglobin levels were associated with better overall health and physical functioning. Patients with significant anemia had significantly lower scores for overall health, physical functioning, and role functioning, which reflects the ability to carry out usual activities, than those without significant anemia, the data showed.
On the QLQ-AA/PNH, higher hemoglobin levels were associated with better scores for physical functioning, fatigue-related activity, and illness intrusiveness, a measure of how much PNH interferes with daily life. Patients with significant anemia had significantly worse scores for illness intrusiveness, fear of disease progression, feelings of stigma, and physical, emotional, and cognitive functioning than those without significant anemia, the data showed.
Given the rarity of PNH, this represents one of the larger prospective datasets with detailed [patient-reported outcome] assessment in a real-world setting.
Fatigue scores on both questionnaires were strongly correlated, but fatigue was not significantly associated with hemoglobin levels or anemia status. Greater fatigue, however, was strongly associated with poorer quality of life across most of the areas assessed.
In further analyses, fatigue emerged as the main factor independently associated with poorer quality of life, such as poorer physical, emotional, and cognitive functioning, greater interference of PNH with daily life, and greater feelings of stigma.
“This real-world study in patients with PNH receiving complement inhibitor therapy confirms that anemia, but not residual hemolysis, is associated with impaired [quality of life],” the researchers concluded.
The team added that “fatigue emerged as a major determinant of [quality of life] independent of [hemoglobin] levels, supporting broader therapeutic strategies addressing overall disease burden.”
The researchers noted the small numbers in the study as a limitation. “However, given the rarity of PNH, this represents one of the larger prospective datasets with detailed [patient-reported outcome] assessment in a real-world setting,” the team noted.
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