Signs and Symptoms
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. Over time, symptoms experienced can change.
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. Some of the more common symptoms are listed below:
Haemoglobinuria
Dark or black urine. This occurs due to the destruction of red blood cells (haemolysis) that occurs in the circulation releasing haemoglobin 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 an investigation to look for bleeding.
Difficulty swallowing and abdominal pain
As PNH red blood cells are destroyed, their contents, particularly the haemoglobin, are released into the circulation. Haemoglobin binds to nitric oxide, 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.
Kidney damage
This can vary from those mildly affected to kidney failure requiring dialysis treatment (this severity is very rare). 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 this can cause a sudden (acute), but usually temporary, kidney failure. It is important that patients drink plenty of fluid to keep the kidneys well hydrated and to reduce the risk of acute kidney problems.
Anaemia
Anaemia occurs commonly in PNH due to the constant destruction of red blood cells. Anaemia causes increased tiredness, fatigue and breathlessness.
Erectile dysfunction
Around half of men with PNH are affected by erectile dysfunction.
Fatigue
Fatigue and tiredness are very common. 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 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 to a substance called bilirubin, which is a breakdown product of haemoglobin and is usually processed by the liver. When the level of haemolysis is very high, the liver has difficulty processing the bilirubin quickly enough, leading to jaundice.
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.
Blood clots
Blood clots (thromboses) are a common complication 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 their extent. Clots can occur anywhere, including in unusual places, such as in the veins of the liver and around the brain.