Paroxysmal Nocturnal Haemoglobinuria (PNH)
Paroxysmal nocturnal haemoglobinuria (PNH) is a rare, acquired blood condition in which red blood cells break down earlier than normal.
Overview
Paroxysmal nocturnal haemoglobinuria (PNH) is a rare, acquired blood condition in which red blood cells break down earlier than normal. This process is called haemolysis. In PNH, part of the body's immune defence system (called the complement system) mistakenly attacks red blood cells. When these cells break down, haemoglobin (the protein that carries oxygen) is released into the bloodstream. PNH can also increase the risk of blood clots and may affect the bone marrow's ability to produce blood cells properly. PNH is not usually inherited. It develops due to a genetic change that occurs during a person's lifetime in blood-forming stem cells in the bone marrow.
Causes and Genetics
PNH is caused by an acquired change (mutation) in a gene called PIGA within blood stem cells in the bone marrow. This change prevents blood cells from producing certain protective proteins on their surface. Without these protective proteins, red blood cells become vulnerable to attack by the complement system and break down prematurely. Because the mutation occurs after birth in bone marrow cells, PNH is not usually passed down to children.
Symptoms and Features
Symptoms can vary widely. Some people have mild disease, while others experience serious complications.
Characteristic Symptoms and Features
- Breakdown of red blood cells (haemolysis): dark or red-coloured urine (often more noticeable in the morning), fatigue, shortness of breath, pale skin and jaundice (yellowing of the skin or eyes)
- Anaemia: low haemoglobin levels can cause tiredness, weakness and dizziness
- Blood clots (thrombosis): PNH increases the risk of blood clots, which may occur in unusual locations such as the abdomen, liver or brain. Blood clots are one of the most serious complications of PNH
Other Associated Symptoms and Features
- Abdominal pain
- Difficulty swallowing
- Headaches
- Erectile dysfunction
- Easy bruising or bleeding if platelet levels are low
- Increased risk of infections if white blood cell levels are reduced
Some individuals may also develop bone marrow failure, which can overlap with conditions such as aplastic anaemia. Symptoms may fluctuate over time.
Treatment
Regular monitoring of blood counts and clot risk is essential. Vaccinations are important before starting complement inhibitor therapy, as blocking part of the immune system increases susceptibility to certain infections. Patients are usually managed through specialist haematology centres.
Research and Future Directions
Research has led to major advances in complement inhibitor therapies, including longer-acting treatments and medications targeting different parts of the complement pathway. Ongoing studies aim to improve convenience, reduce breakthrough haemolysis and further lower clot risk. Researchers are also exploring gene-based approaches and improved management strategies for bone marrow failure associated with PNH. Advances in treatment have significantly improved life expectancy and quality of life for people living with PNH.