How can people living with PNH improve their lives?

Introduction to PNH.

PNH stands for Paroxysmal Nocturnal Hemoglobinuria. It is a rare blood disease that impacts the bone marrow and blood cells. PNH is a complex illness, but we'll explain its causes, symptoms, testing, and diagnosis in simple terms.

Red blood cells in PNH patients

What does PNH mean?

• Red blood cells in PNH patients are more easily broken and less stable. In PNH, the bone marrow fails to produce red blood cells that contain a protein that protects them from the immune system. When the body doesn't have this protein, its defense system attacks these red blood cells and breaks them apart. This procedure is known as hemolysis.
• PNH patients experience issues with their bone marrow, leading to the destruction of their red blood cells. There is a link between it and aplastic anaemia, a rare disease in which bone marrow loss makes it difficult for the body to produce enough new blood cells.

What effects does PNH have on the body?

• Too many red blood cells are lost too quickly, resulting in a shortage of these cells in the body. Many of the signs of PNH are caused by this lack of new blood cells. One of the most obvious signs is hemoglobinuria, which means that the urine looks dark or red because of haemoglobin from the dead red blood cells, especially in the morning. Hemoglobinuria is a very scary sign that can help doctors figure out if someone has paroxysmal nocturnal hemoglobinuria.
• Due to PNH anemia, other signs include feeling worn out, short of breath, and pale. Some people may also experience stomach pain, difficulty eating, and blood clots, all of which can lead to more serious health issues. 

Problems with the bone marrow and PNH

Aplastic anemia is a bone marrow disease that cannot produce enough new blood cells. PNH is closely linked to this disorder. Individuals with PNH may have previously experienced aplastic anemia, or they may develop it in the future. Because of this link, understanding and diagnosing PNH is important for better management and treatment of these related diseases.

Why does PNH happen?

A change in a gene called PIGA leads to paroxysmal nocturnal hemoglobinuria. This gene is necessary to make the protective protein that stops hemolysis. This abnormality is not passed down from parent to child; it happens on its own in some people. This mutation renders the affected blood cells easy targets for the body's immune system. This gene mutation is what causes the signs and complications of PNH blood disease.

How to Diagnose and Treat PNH

• People with PNH are often given blood tests to look for signs of hemolysis and other problems with their blood cells. 
• There is a test called flow cytometry that can find the missing protective proteins on the surface of blood cells. Click here to find out more about how to test for PNH.
• Managing symptoms and avoiding problems are the main goals of treatment for PNH blood disease.
•  This can include medicines that stop bleeding, blood transfusions for people with serious PNH anemia, and even bone marrow transplants in some cases. 
• You should always talk to your doctor about your treatment choices.

How PNH Can Cause Thrombosis

When blood thickens and sticks together, it is referred to as a clot. It's a normal process that helps stop bleeding, but it can be dangerous when clots form in the veins or arteries. This type of condition is called thrombosis. Several things can cause this unwanted bleeding to happen in PNH.

Red Blood Cells Being Killed

• Red blood cells are always being killed in PNH. When these cells split, they release chemicals into the bloodstream that cause it to clot. One of these is hemoglobin, which can hurt the walls of blood vessels and make them sticky, which makes clots more likely.

Activation of Platelets

• Platelets are small cellular fragments that aid in blood clotting. IIn PNH, platelets can become overly active and easily adhere to one another. Since PNH is associated with bone marrow issues, clots are more likely to form.

Add to System Activation

• Complement is a component of the immune system that helps eliminate germs and damaged cells. When someone suffers from PNH, their immune system attacks red blood cells, which causes swelling in the body. This swelling can also lead to blood clots.

Getting rid of nitric oxide

• NIO is a molecule that helps keep blood vessels open and stops blood clots from forming. Red blood cells die in PNH and release haemoglobin. Haemoglobin binds to nitric oxide and makes it less available. This condition makes blood vessels thin and raises the risk of clotting.

Also, read https://www.icliniq.com/articles/blood-health/paroxysmal-nocturnal-hemoglobinuria.

Why does paroxysmal nocturnal hemoglobinuria happen at night?

The "nocturnal" aspect of paroxysmal nocturnal hemoglobinuria (PNH) refers to the increased presence of hemoglobin in the urine that occurs while a person sleeps, making this condition most noticeable in the morning. This happens because hemoglobin is released when red blood cells are killed in PNH. Because people do not urinate at night, their urine becomes more concentrated by morning when they first use the restroom. This makes the dark colour from the hemoglobin build-up easier to see. TThe destruction of red blood cells that causes this sign to appear most prominently at night also occurs during the day.

The amount of hemoglobin increases because red blood cells are destroyed while people with PNH sleep, causing hemoglobin to accumulate in the bladder. When a person doesn't go to the bathroom for a long time, the urine containing this hemoglobin becomes more concentrated.

Changes that can be seen include a level of hemoglobin that causes the urine to appear red, brown, or dark, indicating hemoglobinuria, which is most noticeable upon waking.

Hemolysis, the breakdown of red blood cells, is not limited to occurring at night, despite the term "nocturnal" in its name referring to when the symptoms can be observed. The term "nocturnal" in the name indicates when the sign is visible, rather than when the underlying process occurs.

Thrombosis in PNH: Signs and Treatment

When you have thrombosis, the affected area will hurt, swell, turn red, and feel warm. Between 15% and 30% of individuals with PNH experience blood clots. Recognising these symptoms early is critical for getting help and managing them on time. Managing thrombosis in PNH involves both preventing clots from forming and treating them when they occur.

Treatments 

The video about Advances in Science and Treatment of PNH

To treat PNH, most doctors try to ease the symptoms and prevent problems from happening.  How you are treated will depend on how severe your symptoms and illness are.

 If you only have a few signs of anemia, you may need to take certain actions:

 Folic acid can help your bone marrow, make more healthy blood cells

 Extra iron to help the body make more red blood cells

Soliris contains eculizumab.  This medicine stops red blood cells from breaking down.  Blood clots can be avoided, anemia can get better, and people may not need blood donations at all.  It may make you more likely to get meningitis, so you might need to get protection against it.

Empadelli, or pegcetacoplan, is a targeted therapy that can be given to people who have never been treated before or who are moving from eculizumab or revulizumab.

Ravulizumab (Ultomiris).  Ravulizumab is very much the same as eculizumab, but it has been shown to last longer.  Patients no longer need treatments every two weeks; they only need six or seven a year.

These are some other treatments:

These treatments include blood transfusions.  These treatments help manage anemia, the most common issue associated with PNH.

 These treatments aim to reduce blood levels.  These drugs lower the risk of blood clotting.

Stem cell transplant from bone marrow.  This is the only way to treat PNH.  You can get one if you can get a healthy person, like a brother or sister, to give you stem cells to replace the ones that are dying in your bone marrow.  These aren't "embryonic" stem cells.

Doctors usually only give bone marrow transplants to young people with severe PNH because they are very dangerous to their health.  If your doctor says it might help you, talk to them about the pros and cons.

If your PNH doesn't get better with the normal care, you might want to ask your doctor if you can join a clinical trial.  New ways to treat PNH are being tried out in these tests before they become available to everyone.  Before you sign up, talk to your doctor about what's involved and what you should think about.

Living with PNH

People who have PNH need to see a doctor regularly and be monitored to keep their symptoms under control and avoid complications. Getting help from medical professionals and talking to other people who have PNH can make a big difference in how well you handle this situation.

Conclusion

Rare and dangerous, Paroxysmal Nocturnal Hemoglobinuria is caused by a single genetic mistake in a stem cell.  Things have changed in the world today.  Complement-inhibiting therapies have transformed PNH into a chronic illness that many people can manage. These therapies have greatly reduced the most dangerous complications of the disease and improved the quality of life.