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A panel of experts discusses the nuances of treating paroxysmal nocturnal hemoglobinuria in older patients, focusing on comorbidities and complications.
Since 2007, complement-inhibiting drugs have enabled people with paroxysmal nocturnal hemoglobinuria (PNH) to live longer, more normal lives.
In the second of this two-part series, Physician’s Weekly (PW) spoke with Elizabeth Bowhay-Carnes, MD, Ryotaro Nakamura, MD, and Roy E. Smith, MD, about the nuances of managing PNH in older patients.
PW: How do comorbidities affect the trajectory of PNH?
Dr. Smith: Hemolysis can lead to anemia and severe fatigue, making it impossible for people to work and complete their daily activities. They can develop thrombosis due to hemolysis and renal failure due to PNH.
Comorbidities are important, especially in older patients. Age increases the risk for thrombotic events and decreases renal function. Some older patients develop bone marrow abnormalities, all of which can be exacerbated by PNH. Some older patients with PNH may be more predisposed than younger patients to developing significant secondary comorbidities.
Older patients can develop severe anemia due to hemolysis. Anemia can predispose older patients to heart attack, stroke, and overwhelming fatigue, the cause of which may take years to ascertain.
Dr. Nakamura: Patients who have multiple comorbidities, which tend to increase with age, have more difficulty withstanding PNH-related complications such as active hemolysis and severe anemia.
PW: Are older patients less likely to be diagnosed with PNH?
Dr. Smith: A person may have PNH long before it’s diagnosed. Twenty years ago, PNH was described as a disease that appears in the teenage years or early twenties. Now, it’s found more often in older people.
Dr. Bowhay-Carnes: Not necessarily. PNH is underdiagnosed because it’s rare, and patients present with anemia. Older patients have other factors that can cause anemia, so anemia due to PNH may be attributed to something else.
Dr. Nakamura: I don’t think so. The diagnosis of PNH using flow cytometry is not very controversial. What is difficult is when patients have concurrent or history of aplastic anemia, as Dr. Bowhay-Carnes noted, in which part of the anemia may be due to hemolysis (PNH) and part may be due to production failure (aplastic anemia). These clinical dilemmas are not age-dependent, though.
What are the most important areas for further research?
Dr. Nakamura: The data specific to older patients are limited. Natural history and registry data would help us better understand long-term outcomes and complications in these patients.
Dr. Smith: The focus in new drug development is primarily on inhibition of various portions of the coagulation cascade.
The current treatment of choice for some patients who develop bone marrow failure is bone marrow transplant, an aggressive therapy. We transplant bone marrow in people in their seventies, but comorbidity and mortality with transplants increase with age. Investigating alternative treatments short of bone marrow transplant is important.
What else should clinicians know about patients who are older?
Dr. Smith: In a person with any evidence of Coombs-negative hemolysis, PNH should be investigated immediately. Breakthrough hemolysis is common in patients treated for PNH, and the newest agents specifically treat breakthrough hemolysis. All patients should be seen at centers that regularly treat PNH.
Dr. Nakamura: As PNH often occurs in younger people, they go through school, work, marriage, and having families during active therapy. Their compliance and life priorities may change over time. Physicians need to discuss these issues with patients and their families and provide the most beneficial and practical treatment options.
Dr. Bowhay-Carnes: It’s exciting to have choices and the ability to personalize PNH treatment to individual patients, but we’re still hoping for a cure. Numerous new drugs are in development, and I’m excited about what the future holds.
Part one of this two-part series can be found here.
