It’s natural to imagine the worst if you’re diagnosed with a rare disease like paroxysmal nocturnal hemoglobinuria (PNH). But does PNH really affect your life expectancy? Let’s look at the prognosis (outlook) for PNH and explore the recent advances in treatment that have significantly improved outcomes for people living with PNH.

PNH is a rare condition where the body’s immune system accidentally destroys its own red blood cells. This process often happens during the night, which can cause someone with the condition to wake up with dark-colored urine because of the breakdown of these cells. PNH can cause severe fatigue and shortness of breath, and it increases a person’s chances of developing blood clots.

What’s the Life Expectancy for People With PNH?

Twenty years ago, a PNH diagnosis meant a high risk of early death. The only treatment options were blood transfusions. People with PNH lived an average of 14.6 years after symptoms began, with a typical range between 10 and 22 years.

But then, an important discovery changed the prognosis for people with PNH. In the mid-2000s, scientists developed a new type of medication called complement inhibitors.

The First Complement Inhibitor

The complement system is a group of proteins in your immune system. Think of the complement system as little warriors fighting off invaders like viruses and bacteria. Sometimes, these warriors are fighting so hard that they start hitting the wrong targets — your red blood cells.

In PNH, the red blood cell’s shields are broken because of a mutation (change) in a gene called PIGA. So, people with PNH can’t defend against the complement system’s attacks. Red blood cells are destroyed in a process called hemolysis. That’s where complement inhibitors come in.

Complement inhibitors are medications that stop the complement system from destroying red blood cells. In 2007, the United States Food and Drug Administration (FDA) approved eculizumab (Soliris) as the first complement inhibitor to treat PNH.

Since eculizumab came to market, the life expectancy for people with PNH has very much improved. Now, most people who receive treatment for this blood disorder can expect to live a similar length of time to those without PNH.

What Causes Death in PNH?

The main cause of death in people with PNH is thrombosis (blood clots). This PNH complication occurs blood begins to clot (thicken into a semisolid state) in your blood vessels, potentially blocking the vessels from regular blood flow. Thrombosis (also called thromboembolism or thrombotic events) can happen in the liver, abdomen, or brain. Clots can also travel to the lungs, a condition known as pulmonary embolism. Up to 40 percent of people with PNH eventually develop thrombosis. It’s even more common in people with PNH hemolysis.

The second most common cause of death in people with PNH is related to bone marrow failure. Bone marrow, the soft spongy tissue inside your bones, makes new blood cells to replace those killed by the complement system. But in people with PNH, the bone marrow can’t always keep up with the demand. Bone marrow failure increases mortality risk in several ways:

• Cardiovascular complications due to decreased red blood cells
• Severe infections caused by decreased white blood cells
• Major bleeding episodes due to decreased platelets

Two types of bone marrow failure that are common with PNH are called aplastic anemia and myelodysplastic syndrome (MDS).

Other serious complications of PNH that might affect your quality of life or survival are:

• Pulmonary hypertension
• Dysphagia (difficulty swallowing)
• Dyspnea (difficulty breathing)
• Abdominal pain
• Kidney disease
• Erectile dysfunction
• Leukemia

What Aspects of PNH Increase Risk of a Shorter Lifespan?

Some aspects of PNH raise the risk for a shorter lifespan, including thrombosis, leukemia, and MDS. Developing any of these complications of PNH is associated with worse outcomes.

As PNH progresses, your white blood cell, red blood cell, and platelet levels can become too low. This is called pancytopenia, and it also increases your risk of early death. Your outlook may also be worse if PNH begins when you’re older than 55 years of age.

Research indicates that where you’re from may play a role in the course of your PNH as well. Studies compared people with PNH in Japan and America. They found that Japanese people survived longer than Americans. This difference in life expectancy might be because Americans were much more likely to have blood clots.

Many of these studies on risk factors were done before the discovery of complement inhibitors. Doctors talk about this as the “pre-complement inhibitor era.” These medications can help overcome risk factors and improve outcomes for people with PNH.

Let’s learn more about the treatments that can manage your risk with PNH.

Manage Your Risk With Targeted Treatment

One effective strategy that may improve your life expectancy and prognosis with PNH is to start taking complement inhibitors. These targeted medications reduce or prevent hemolysis and lower the risk of thrombosis. Complement inhibitors may also improve kidney function. Even people with complex PNH have survival benefits with eculizumab. Eculizumab also improves the quality of life for people with PNH and significantly reduces the need for frequent blood transfusions.

Eculizumab was a major step in treating PNH, but it still has its limits. If you take eculizumab, you’ll have to have infusions every two weeks for the rest of your life. That can be an inconvenience and quite expensive for many people. Eculizumab is also not perfect — you may still experience hemolysis — known as breakthrough hemolysis — even if you take this medication regularly.

New Complement Inhibitors

The FDA has approved new complement inhibitors, including ravulizumab (Ultomiris), iptacopan (Fabhalta), and pegcetacoplan (Empaveli). So far, they have shown promise for improving the life expectancy and quality of life for people with PNH. Long-term research will help hematology specialists better understand how these novel medications affect people with PNH over time.

These new medications all add up to a longer life expectancy for those who treat their PNH with complement inhibitors. A 2021 study cited in the journal Blood looked at thousands of people with PNH. They found that people who took complement inhibitors had an 82 percent chance of surviving for 20 years. In contrast, people who were never treated had a 69 percent chance of surviving for the same period.

Other Treatments

You may also need to treat complications of PNH, like thrombosis. Anticoagulants — also known as blood thinners — aim to prevent blood clots, but they don’t seem to be successful at treating thrombosis in PNH on their own. You’ll likely take a combination of anticoagulants and complement inhibitors to manage thrombosis in the short term. Your doctor might want to keep you on anticoagulants after your thrombosis has passed to lower your risk of another blood clot.

Complement inhibitors don’t treat bone marrow failure. People with serious cases of bone marrow failure may be recommended to receive bone marrow transplants. Bone marrow comes from a donor, ideally a sibling or someone with a similar immune system to yours that can be matched to you through a bone marrow registry. While you wait for a donor, complement inhibitors can manage hemolysis.

PNH is a long-term disease with a risk of life-threatening complications. But with the recent invention of complement inhibitors, most people with PNH can live longer, healthier lives. To improve your life expectancy, make sure to follow your doctor’s instructions to keep your PNH well managed. Keep up with all recommended appointments to help find any PNH complications early, and talk to your health care team if you have any changes in symptoms.

Talk With Others Who Understand

On myPNHteam, the social network for people with paroxysmal nocturnal hemoglobinuria and their loved ones, members come together to ask questions, give advice, and share their stories with others who understand life with PNH.

Do you have concerns about how PNH may shorten your lifespan? What steps do you take to lower your risk of serious complications? Share your experience in the comments below, or start a conversation by posting on your Activities page.