What is PNH?

Paroxysmal Nocturnal Haemoglobinuria (PNH) is an acquired rare blood disorder that affects the bone marrow and the cells it produces. PNH is not hereditary but instead develops when stem cells in the bone marrow acquire a mutation causing the development of defective blood cells. The damaged cells lack protective proteins on their surface, making them vulnerable to attack by the part of the immune system called the complement. This attack leads to the premature destruction of red blood cells — known as haemolysis — which causes a reduction in haemoglobin levels and causes many of the symptoms of PNH. PNH affects white blood cells and platelets as well as red blood cells. Abnormal white blood cells may contribute to immune and infection‑related issues, while abnormal platelets are linked with a higher risk of blood clots (thrombosis).

Video courtesy of the PNH National Service

Understanding PNH Terminology

Understanding the language used around PNH can make appointments and test results much easier to navigate. This guide explains some key PNH terms in easy-to-understand language.

This refers to dark urine that is often seen in PNH patients first thing in the morning. The dark colour comes from blood in the urine due to haemolysis. Although PNH refers to ‘nocturnal haemoglobinuria’ in its name, not everyone experiences this sign, and symptoms often vary among individuals.
Haemoglobin is a protein inside red blood cells that carries oxygen from the lungs to the rest of the body. If haemoglobin levels are low there is less oxygen being carried around the body which can lead to symptoms like fatigue, shortness of breath and headaches.
Haemolysis is the process where red blood cells break down earlier than they should, releasing haemoglobin into the bloodstream.
In a healthy body, red blood cells live for about 120 days while PNH red blood cells may last only a few days or weeks. During haemolysis, red blood cells are destroyed too soon, which can reduce the blood’s ability to carry oxygen around the body. This can lead to the symptoms of PNH that many patients experience.
The PNH clone size shows what percentage of a person’s blood is made up of PNH cells. Patients typically have varying ratios of normal and PNH blood cells. PNH cells, lacking protective surface proteins, are produced by abnormal bone marrow stem cells while normal blood cells continue to be produced by normal (non-mutated) stem cells.
- A low clone size means fewer PNH-affected cells
- A high clone size means more PNH-affected cells
Clone size is most accurately measured using white blood cells, specifically granulocytes and monocytes, rather than red blood cells. This is because white blood cells are not destroyed as quickly as red blood cells and therefore provide a more reliable result.
The clone level helps guide treatment decisions, identify patients who may benefit from complement-inhibition therapy and allows clinicians to monitor the condition’s stability or progression over time. Clone size may change over time and it does not always reflect how severe a patient’s symptoms are.
Intravascular haemolysis (IVH) means red blood cells are being destroyed inside the blood vessels.
In PNH, red blood cells are not properly protected and can be attacked by the immune system’s complement pathway. When this happens, the cells break apart in the bloodstream and release haemoglobin.
IVH can contribute to:
- Anaemia
- Fatigue
- Dark or discoloured urine
Extravascular haemolysis (EVH) means red blood cells are destroyed outside the bloodstream, mainly in the liver and spleen.
In PNH, some red blood cells become marked by the immune system and are then removed by these organs instead of breaking apart in the blood vessels.
EVH can:
- Cause ongoing anaemia
- Occur even when intravascular haemolysis is controlled
A thrombosis is the formation of a blood clot inside a blood vessel. A thrombosis can slow or block the flow of blood, which may affect the organs or tissues it supplies. In people with PNH, abnormal red cells, white cells and platelets contribute to an increased tendency for clots to form. Clots most often occur in veins but can happen in other parts of the body. Healthcare teams always monitor for clots in PNH patients carefully.

PNH Symptoms

Every person with PNH experiences symptoms differently — some may be mildly affected, while others may face serious complications.

Complications can vary widely, and not all individuals with PNH will experience the same issues. Regular monitoring with a healthcare team is important.

Some common PNH symptoms are listed below.