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Understanding the disease burden of PNH

Journal: Annals of Hematology

The goal

What did scientists want to find out?

In 2020, a group of scientists set out to update a 2014 report using data from the International PNH Registryinternational pnh registryThe International PNH Registry is a worldwide collection of data of more than 5,000 volunteer patients with PNH. The goal of the Registry is to help improve understanding of PNH to allow doctors to better manage the disease in their patients. about PNH patients.

The report included how long patients had PNH, their clone sizes, and their symptoms. It also looked at their disease burden, or the impact of PNH on their lives and their health. The researchers also wanted to find any new, relevant insights to share.

The method

How, where and when did they look for information to analyze?

The scientists reviewed data from 4,948 patients enrolled in the Registry. Of those, 4,439 had answered enough questions to be included in the newer study. This is almost three times as many as in 2014 – making it the largest group of patients with PNH ever studied.

The researchers wanted to know how many patients had experienced:

  • High disease activity

  • Blood clots

  • Bone marrow failure

  • Red blood cell transfusions

  • Using other medicines

  • Fatigue
    (according to patients)

  • Impacted quality of life
    (according to patients)

  • PNH symptoms
    (reported by their doctors)

Patients were divided into three groups based on their clone sizeclone sizeThe percentage of blood cells impacted by PNH. A large clone size means you have a high percentage of blood cells that can be attacked by the complement system, which may lead to more severe symptoms.:

  • Clone size smaller than 10%

  • Clone size smaller than 10%

  • Clone size smaller than 10%

Researchers then looked at the link between high disease activity and PNH clone size, which had not been done before. High disease activity was defined as hemolysis and at least 1 of the following:

  • FatiguefatigueA feeling of being overtired or exhausted, with low energy and a desire to sleep, which interferes with normal daily activities. Fatigue is one of the most common symptoms of PNH.

  • HemoglobinuriahemoglobinuriaThe presence of hemoglobin in the urine caused by the destruction of red blood cells.

  • Abdominal pain

  • DyspneadyspneaDifficulty breathing or shortness of breath. (difficulty breathing)

  • AnemiaanemiaA condition that occurs when there are not enough red blood cells to effectively carry oxygen around the body, which can cause fatigue, shortness of breath, headaches, and other symptoms.

  • Major adverse vascular events (like blood clotsblood clots)

  • Difficulty swallowing

  • Erectile dysfunction

Finally, the researchers examined the relationship between clone size and disease burden. This means PNH’s impact on patients’ lives and their health.

The findings

What did the researchers learn?

Most lab results showing greater disease burden were related to PNH clone size.

More than half of patients had high disease activity, found to be related to clone size

Almost ten percent of patients with small clone sizes also had high disease activity

More patients in this study than the earlier study had experienced bone marrow failure (when the bone marrow can’t make the amount of blood cells the body needs).

Most patients with both PNH and bone marrow failure had the smallest of the three clone sizes. Less than 10 percent had the largest clone size.

Hemolysis was found in patients of all clone sizes. Hemolysis is associated with higher risk of events like blood clots, the leading cause of death in PNH patients.

Over half of patients
(56 percent) had hemolysishemolysisThe “breaking apart” of red blood cells. It can occur when the immune system attacks these cells as though they were dangerous viruses or bacteria. When red blood cells break open, hemoglobin is released. Hemolysis causes many of the symptoms of PNH.

Almost half (43 percent) had impaired kidney function. The group with the smallest clone sizes had a higher rate of kidney failure. This might be because these patients had the highest rates of:

  • bone marrow failure

    89%

  • immunosuppressive therapyimmunosuppressive therapyImmunosuppressive therapy uses medications to lower your body's immune response. For example, immunosuppressive therapy can help prevent your immune system from attacking your bone marrow, allowing bone marrow stem cells to grow, which can help raise blood counts.

    59%

In the newer study, more patients overall had a history of red blood cell transfusions.

The researchers found no link between clone size and transfusions. This may be because more patients in this study had experienced bone marrow failure, which is often treated with transfusions.

  • The scientists suggest that patients with larger clone sizes might get transfusions for anemia caused by their complement systemcomplement systemThe complement system, also referred to as the complement cascade, is an army of more than 50 different proteins that work together to get rid of dangerous cells and fight infection. destroying red blood cells.

  • Those with smaller clone sizes might need them for anemia caused by their bone marrow not producing enough red blood cells.

  • Finally, like the earlier study found, PNH patients reported more fatigue and lower quality of life than adults without PNH.

The takeaway

What did the researchers conclude from the study?

  • In general, untreated patients with larger PNH clone sizes had higher disease burden — but many patients with smaller clone sizes also experienced symptoms and adverse events.
  • Based on this, doctors may need to emphasize disease symptoms and consider treatment for these patients.
  • Since this study observed many different clone sizes, more data are needed to confirm the best approach for each individual patient with PNH.
  • Fatigue was the only disease burden measure that was not associated with clone size. Based on this, fatigue may not be a reliable sign of PNH severity based on clone size. Patients with small clone sizes can have severe fatigue.
  • Kidney dysfunction is common in patients with PNH. More study is needed to understand the relationship between PNH and kidney disease. For instance, certain therapies for anemia or bone marrow failure might actually harm the kidneys.
  • The findings confirmed that PNH places a significant burden on patients. Future studies about disease burden, fatigue, and quality of life could shed more light on how PNH affects patients from day to day.
  • This study can help doctors understand PNH overall, especially the relationship between disease activity and PNH clone size, to help them better manage PNH in their patients.
Please note: The information on this page is meant to be informational only and is not intended to replace medical advice. Always talk to your healthcare provider about any questions you may have on PNH, its symptoms or treatment.
  • Title: Baseline clinical characteristics and disease burden in patients with paroxysmal nocturnal hemoglobinuria (PNH): updated analysis from the International PNH Registry
  • Journal: Annals of hematology, 99(7), 1505–1514.
  • Written by: Schrezenmeier, H., Röth, A., Araten, D. J., Kanakura, Y., Larratt, L., Shammo, J. M., Wilson, A., Shayan, G., & Maciejewski, J.P
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Please note: The information on this page is meant to be informational only and is not intended to replace medical advice. Always talk to your healthcare provider about any questions you may have on PNH, its symptoms or treatment.