Paroxysmal Nocturnal Hemoglobinuria (PNH)

Not everyone who has PNH is affected by it in the same way. Some people experience no symptoms, and some have mild symptoms, while some may have severe symptoms and need medication and/or blood transfusions. Additionally, over time the symptoms experienced by a person living with PNH may change.

It is important to note that people with no or few symptoms can still suffer from complications of PNH itself. Some people will only experience symptoms when an episode of severe red blood cell breaking (hemolysis) is occurring, and others may experience symptoms constantly. Events that can trigger an episode of severe hemolysis include infections, trauma, surgery, exercise, lack of sleep, or stress.

Symptoms of PNH occur because of the destruction of the body’s red blood cells (hemolysis) by complement. Chronic hemolysis is central to all symptoms associated with PNH. Mild hemolysis can cause symptoms such as fatigue, rapid heartbeat, headaches, chest pain, and difficult breathing or breathlessness. More severe hemolysis can cause additional symptoms, such as disabling fatigue, difficulty swallowing (dysphagia), abdominal or back pain, and erectile dysfunction. Chronic hemolysis can result in the development of blood clots (thromboses) and kidney disease.

People with PNH are more likely to get a blood clot in their lifetime than people without PNH. People with PNH tend to get blood clots in less common parts of the body, such as the abdomen (belly) or the brain. Places in the abdomen where blood clots may occur include: the spleen, the major vein leaving your liver (called Budd-Chiari syndrome), or the intestines (called ischemia). Symptoms of a blood clot in the abdomen may include: fluid build up or swelling in the belly, feeling of warmth in the area where the blood clot is, and pain in the area of the blood clot. Some people living with PNH may also experience blood clots in the veins covering their brain. This can cause the brain to stop working well, and potentially cause: a very bad headache, trouble speaking, seeing, or moving parts of the body, or changes in vision.

Additionally, PNH causes some degree of bone marrow dysfunction, which can affect how blood cells are developed. If the bone marrow dysfunction is mild, then there may be no symptoms or only mild symptoms. People with severe bone marrow dysfunction may have low levels of red blood cells (anemia), low levels of white blood cells (leukopenia), or low platelets (thrombocytopenia), or even all three (pancytopenia). People with anemia may experience tiredness, weakness, lightheadedness, dizziness, pale skin, difficulty breathing (dyspnea) and chest pain. People with leukopenia are at an increased risk of infections. People with thrombocytopenia are more likely to have excessive bruising and bleeding.

PNH can affect anyone at any age, but it is most commonly diagnosed in young adults in their 20s or 30s. Diagnosing PNH may be challenging for several reasons. First, PNH is a rare disease, and many doctors have never seen a case of it. Additionally, the symptoms and severity of PNH may vary widely between different people, meaning that there is not one uniform, distinguishing presentation of PNH. For some people living with PNH their symptoms may cause minimal disruption to their daily lives, whereas for others their symptoms may cause them to be severely limited in their ability to work, socialize, and otherwise function in everyday life. Usually, symptoms tend to gradually appear, so it may take years for a person living with PNH to be diagnosed.

To confirm a diagnosis of PNH, a blood sample is sent to a specialized laboratory to check whether it contains PNH blood cells using a test called flow cytometry. Flow cytometry is used to look at blood cells and identifies PNH cells (those missing proteins that protect the cell from the complement system). This test shows the percentage of both red PNH cells and white PNH cells in the blood. FLAER is a new type of flow cytometry testing that may also be used to confirm the diagnosis of PNH.

Additionally, several other tests are commonly performed when diagnosing PNH to rule out complications of PNH and assess its severity. These tests may include:

• Bone marrow biopsy
• Blood tests, including a CBC (complete blood count). This measures the number of each type of blood cell in your sample.
• Ultrasound, CT, MRI or V/Q scan (if your doctor is concerned for blood clots (thrombosis)).
• Tests to look for evidence of hemolysis (red blood cell destruction) in your body. These tests may include:
  • Bilirubin (a by-product of hemoglobin. Tends to increase in situations of increased red blood cell destruction).
  • LDH (lactate dehydrogenase). LDH increases with more hemolysis.
  • These are the number of young red blood cells in your bone marrow. This looks at how many new red blood cells your bone marrow is currently making. Your reticulocyte count tends to be unusually increased if you are experiencing hemolysis.

There are several treatment options available to people who are living with PNH. Depending upon the severity and the progression of the disease, your doctor will determine what treatment is right for you.

Complement Inhibitors

Complement inhibitors work in the treatment of PNH by blocking the complement part of the immune system and making it less active. Complement inhibitors have been found to improve anemia (low red blood cell counts), reduce or eliminate the need for blood transfusions, reduce hemolysis (the breaking apart of red blood cells), reduce the risk of developing blood clots, and reduce symptoms of PNH (such as fatigue) and improve quality of life.

There are different types of complement inhibitors available. C5 inhibitors (Soliris^® and Ultomiris^®) and the C3 inhibitor (Empaveli^®). Soliris^® and Ultomiris^® are either given by IV infusion at the doctor’s office or infusion center, whereas Empaveli^® may be administered subcutaneously (under the skin) as an infusion with a special pump in the home setting or through an Empaveli Injector. Voydeya^TM is an oral tablet and Fabhalta^® is an oral capsule..

Bone Marrow/ Stem Cell Transplant

A bone marrow transplant (BMT) is the only cure for PNH, but it involves significant risks and it may be difficult to find a well-matched donor. Due to advances in the treatment options for people living with PNH, notably medications called complement inhibitors, BMT is not usually recommended as an initial treatment for PNH. BMT is often considered to be a “last resort” for people living with PNH and may only be performed where the patient has an excellent match (siblings are best) or their PNH is life-threatening, or not responding to other treatment options.

A BMT is a procedure where a patient’s own bone marrow is replaced by a healthy matching donor’s bone marrow. Prior to replacing the patient’s bone marrow with donor marrow, the patient may be treated with high doses of chemotherapy to destroy their diseased bone marrow.

There are many complications associated with BMT, notably the risk of developing serious infections, as well as graft vs host disease (GvHD), where the transplanted bone marrow cells attack the patient’s body.

Other Supportive Medications

Medications other than complement inhibitors may be prescribed to help reduce hemolysis and also to try to treat and/or prevent the complications associated with PNH. Some people living with PNH may be prescribed corticosteroids, such as prednisone or dexamethasone, to reduce the rate of blood cell destruction by suppressing the body’s immune system (and therefore complement attack on the blood cells).

Doctors may prescribe growth factors to help increase the number of blood cells in the body. Growth factors are naturally occurring hormones that signal the bone marrow to make more of certain types of blood cells. Man-made growth factors may be prescribed to some people experiencing bone marrow failure to help increase the number of red blood cells, white blood cells, or platelets respectively.

Additionally, anticoagulants, sometimes referred to as blood thinners, such as warfarin (Coumadin^®), enoxaparin (Lovenox^®), apixaban (Eliquis^®), or rivaroxaban (Xarelto^®), may be prescribed to reduce the risk of a blood clot (thrombosis), especially for those people who have already have evidence of blood clot formation.

Blood Transfusions

While blood transfusions won’t cure or treat the underlying disorder in PNH, they can help to relieve some of the symptoms experienced with PNH. Blood transfusions replace blood cells that are lost to hemolysis by the body’s complement system. The most common type of blood cell transfusion in PNH is a red blood cell transfusion, which increases the number of red blood cells carrying oxygen in the body. Blood transfusions are usually given in an outpatient clinic, and it takes approximately 2 hours to infuse 1 unit of blood. Depending upon the severity of PNH and symptoms, people living with PNH may require transfusions occasionally, such as after an episode of breakthrough hemolysis secondary to an illness, surgery or injury, or may routinely require blood transfusions every few weeks or months.

Clinical Trials

Clinical research is currently being conducted to identify new ways to treat PNH. If you or a loved one have PNH, the doctor may recommend that you consider taking part in a clinical trial or research study. People who are usually considered to be good candidates for participating in a clinical trial are those who have not benefitted from the available standard treatments.