Understanding PNH

Patient Voice sat down with Dr. Monika Oliver to learn about paroxysmal nocturnal hemoglobinuria (PNH), a rare and mysterious disease that leads to the premature breakdown of red blood cells.

Photography by Red Earth Photography.

Dr. Oliver is a clinical lecturer in the Division of Hematology and the Division of Apheresis Medicine at the University of Alberta Hospital.

1. What is PNH?

PNH is a rare, acquired, and life-threatening disease of the bone marrow. PNH occurs because of a genetic mutation in the PIG-A gene of a single stem cell. This abnormal stem cell makes multiple copies or “clones” of itself, leading to a population of PIG-A mutant cells in the bone marrow. Some of these mutant PNH stem cells will develop into red blood cells that lack specific protective proteins. In people without PNH, these proteins normally shield red blood cells from destruction with the help of a specific part of our immune system called the complement system. The complement system is a complex group of proteins in the blood that plays an important role in helping us to fight infections.

In patients with PNH, red blood cells break apart prematurely in a process called hemolysis. When hemolysis occurs, we see the multi-systemic effects of PNH. To date, we don’t know exactly why PNH develops in some people and not in others. 

2. How does PNH typically present?

There can be significant variation in the signs and symptoms of PNH that are observed both between patients and in the same patient over time. Some patients may exhibit few or even no symptoms. However, in most patients, PNH can manifest with severe and life-threatening symptoms. Some common symptoms of PNH include fatigue, dysphagia (difficulty swallowing), abdominal discomfort, erectile dysfunction in males, hemoglobinuria (dark, red, or even brown-looking urine), and kidney damage. 

As a result of continuous hemolysis (blood cell breakdown), most patients with PNH will have low hemoglobin levels, which is known as anemia. The symptoms they usually experience as a result of anemia include shortness of breath, weakness, decreased exercise tolerance, and even jaundice (yellowing of the skin or eyes). 

However, the most disastrous complication of PNH is thrombosis, which is a process where blood clots develop in the veins or arteries. Thrombosis can occur both in common places, like the legs and lungs, and in atypical locations, like the abdomen or brain, and can be life-threatening. Nearly half of untreated PNH patients develop a thrombotic complication.

Dr. Oliver is focused on ensuring patients can be diagnosed and treated as early as possible.

3. Why is it important to receive a prompt diagnosis following symptom onset?

Prompt diagnosis is so important because it helps to prevent the long-term complications of PNH, some of which — such as thrombosis — may be fatal or leave patients with irreversible morbidity. Unfortunately, because symptoms of PNH may be non-specific, many health care practitioners may not be attuned to recognizing the presentation. As such, many patients with PNH often experience a significant delay from the time of symptom onset to the time of diagnosis, leaving them vulnerable to developing lifelong complications of the disease. 

4. How is PNH treated? What role can patients play in their care?

Patients with PNH may undergo multiple different treatments depending on the severity of their symptoms, the proportion of PNH-affected cells, and the drug funding structure in the region in which they live.

Most patients will receive supportive treatments to try to manage the complications of PNH and improve symptoms. For example, some patients may receive blood transfusions to manage their anemia, and some will require supplementary folic acid and/or iron, which is needed by the bone marrow to produce new blood cells. Some patients may be on anticoagulants (blood thinners) to treat or prevent blood clots.

However, definitive treatment for PNH is with drugs called complement inhibitors. These medications work by “blocking” or “clamping” the complement system to try to eliminate blood cell breakdown. The complement inhibitors most widely available in Canada currently are in IV form and require frequent administration every two to eight weeks. Unfortunately, patients with PNH require lifelong therapy with complement inhibitors to control their disease, which can be costly and is not covered by many health care systems worldwide.

Finally, although it’s rarely performed, a bone marrow transplant is another treatment option for some patients. While it’s the only curative treatment for PNH, it’s a high-risk procedure with significant morbidity and mortality rates and thus usually reserved for patients with other bone marrow problems in addition to PNH. 

“Many patients with PNH often experience a significant delay from the time of symptom onset to the time of diagnosis, leaving them vulnerable to developing lifelong complications of the disease.”

5. Why is it a hopeful time for Canada’s PNH community?

We have many treatment options coming down the pipeline for patients with PNH. In the past couple of years, there has been an explosion of new therapies that allow us to block the complement system in different ways and also to administer treatments in less intrusive forms. A number of different clinical trials are currently underway, and we’re also seeing promising new drugs that are approved in other countries and which will hopefully be available in Canada within the next few years as we get more data about their safety and efficacy. 

Because PNH is a rare disease, often with a significant lag in diagnosis, PNH patients learn to be incredible advocates for themselves. The PNH patient community has played a critical role in continuing to spread awareness about the disease among the public and medical community and also to create resources to support others living with the disease. 

The PNH community has done so much to drive advances in PNH treatments and to bring new therapies to Canada. It’s an inspiring community, and I feel so fortunate to be part of it!

If you’ve been diagnosed with PNH, either recently or in the past, there's a community of patients, caregivers, and clinicians here to support you. To learn more about PNH, seek support, or access additional resources, please connect with the Canadian Association of PNH Patients and check out their guide on living better with PNH

This initiative was supported by Alexion AstraZeneca Rare Disease. The content was developed by Patient Voice, and the supporter did not influence the final article or editorial themes.