There can be a marked variation in the signs and symptoms observed due to PNH both between patients and in the same patient at different times. Some people exhibit no symptoms whereas others may be affected by a number of very different disease symptoms and complications. Patients with no or few symptoms can still sometimes suffer from complications. These can dramatically affect people’s everyday lives and without treatment some of them can be life threatening. Over time the symptoms experienced by anyone with PNH can change. In some people, symptoms occur all the time and in others only when an episode of haemolysis is experienced. Some of the more common symptoms are listed below:
- Haemoglobinuria – Dark or black urine due to free haemoglobin in the urine. This occurs due to the destruction of red blood cells (haemolysis) that occurs in the circulation so that the red cells effectively burst. This leads to the release of haemoglobin, that is usually packaged inside the red cells, into the plasma (the liquid part of the blood) and this then overflows through the kidneys into the urine. Haemoglobinuria can be confused with haematuria (bleeding into the urine) which often leads to some patients having investigation to look for bleeding.
- Anaemia – Anaemia occurs commonly in PNH due to the constant destruction of red blood cells. It can also be aggravated by bone marrow failure which co-exists in some patients with PNH. Anaemia in turn causes increased tiredness, fatigue and breathlessness.
- Breathlessness – This is in part due to anaemia but can also be experienced due to increased blood pressure in the lungs (pulmonary hypertension) that may occur in PNH. If breathlessness occurs suddenly then it is important to exclude other causes such as infection or blood clots going to the lungs. These are rare but important alternative explanations.
- Difficulty swallowing and abdominal pain – As PNH red blood cells are destroyed, their contents, particularly the haemoglobin, are released into the circulation. Haemoglobin is not meant to be free in the plasma as it binds other gases as well as oxygen. One of these, called nitric oxide, is used by the body to help the muscles of the intestine (amongst other muscles) to work properly. If there is free haemoglobin in the plasma and therefore a low level of nitric oxide this leads to spasm in the muscles of the intestinal/digestive system. This can affect the oesophagus (gullet) causing difficulty swallowing and/or the intestines causing abdominal pain. Occasionally, the abdominal pain is due to a blood clot and this will also need investigations for exclusion.
- Erectile dysfunction – Around half of men with PNH are affected by erectile dysfunction. This also appears to be due to the depletion of nitric oxide by free haemoglobin and is generally worse during an attack of haemoglobinuria.
- Fatigue – Fatigue and tiredness are very common in PNH. Fatigue is something that is difficult to quantify but can be extremely debilitating meaning that some patients at times cannot even manage very mild activity. This is also possibly a symptom of nitric oxide depletion and can occur even when the haemoglobin level is relatively good.
- Jaundice – Yellow discolouration of the sclera (whites of the eye) and the skin due to the continued destruction of red blood cells. The yellow colour is due a substance called bilirubin which is a breakdown product of haemoglobin and is usually processed by the liver. When the level of haemolyis is very high the liver has difficulty processing the bilirubin quickly enough leading to jaundice.
- Kidney damage – This can vary from those mildly affected to kidney failure requiring dialysis treatment (this severity is very rare). The kidney problems in PNH can occur due to the haemolysis, blood clots as well as due to other therapies that might be necessary to treat associated conditions such as aplastic anaemia. Most patients with PNH do not develop significant kidney problems but this needs to be carefully monitored. Occasionally, during an episode of severe haemolysis and haemoglobinuria the kidneys have difficult dealing with the haemoglobin that they are filtering and this can cause a sudden (acute), but usually temporary, kidney failure. It is important during episodes of haemoglobinuria that patients drink plenty of fluid to keep the kidneys well hydrated and to reduce the risk of acute kidney problems.
- Blood clots – Blood clots (thromboses) are a common complication of PNH occurring in up to half of patients. Thrombosis is something we are always keen to exclude as if they occur they need specific treatment and may be serious or even life-threatening. The symptoms of thrombosis are highly variable and depend largely on where they develop and it’s extent. Clots can occur anywhere including in unusual places such as in the veins of the liver and around the brain.