When you get up in the middle of the night, do you notice the colour of your urine? However, this is an important indicator for those living with a rare disease called paroxysmal nocturnal hemoglobinuria (PNH). This condition affects the red blood cells (RBCs) and can lead to a variety of serious symptoms, from blood clots to an increased risk of infection.
In fact, the name itself offers an insight into the condition. Paroxysmal stands for sudden, nocturnal means night, and haemoglobinuria means blood in the urine. In individuals with PNH, the RBCs become abnormally sensitive to the body’s immune system. This occurs due to a mutation in a gene called PIGA. Due to its rarity, the exact incidence is unknown, however, it is estimated that the global prevalence is 15.9 individuals per one million people.
The PIGA mutation in PNH causes red blood cells to break down (or haemolyze) too easily, especially during the night, releasing haemoglobin into the bloodstream. This can lead to a number of symptoms, many of which might initially seem mild or unrelated, such as dark-coloured urine, fatigue, and unexplained bruising. The paroxysmal aspect of PNH refers to the fact that these symptoms can come and go, and often, people with PNH may have stretches of time where they feel completely normal. However, without proper diagnosis and management, PNH can lead to serious complications.
Signs and symptoms
PNH can develop at any age, from early childhood to late adulthood. Records have shown that it can be diagnosed in patients as young as two and as old as 80. Most people with PNH are first diagnosed in their 30s, with most cases occurring between the ages of 30 and 40. Individuals with PNH experience non-specific symptoms, making accurate diagnosis a challenge. Some include:
- Dark-coloured (brown or reddish) urine, often most noticeable in the midnight or morning due to the presence of RBCs
- Fatigue and weakness, that can become debilitating over time
- Shortness of breath
- Headaches
- Unexplained bruising, often seemingly without cause
- Abdominal pain
- Frequent infections
Because many of these symptoms are common in other, less severe conditions, PNH is often underdiagnosed or mistaken for other issues initially. For instance, someone with dark urine might think they’re dehydrated, or someone who is fatigued might assume they just need more rest. However, in the case of PNH, these symptoms persist and worsen over time, prompting further investigation.
Diagnosis often begins with a detailed clinical assessment to identify common symptoms. Initial laboratory tests typically reveal anaemia and signs of RBC destruction (elevated levels of lactate dehydrogenase, low haptoglobin, and increased reticulocyte counts). The key diagnostic tool is flow cytometry, which detects the absence of certain proteins (CD55 and CD59) on RBCs linked to PIGA gene mutation. Additional tests, such as coagulation studies and renal function tests, assess complications, while bone marrow biopsy and genetic testing may be conducted in complex cases to differentiate PNH from conditions.
Importance of awareness
Although rare, PNH has a profound impact on a patient’s quality of life. It leads to severe anaemia primarily due to destruction of RBCs and results in a significant loss of haemoglobin. Additionally, in some patients with PNH, the bone marrow, which is responsible for producing new blood cells, is also affected, leading to bone marrow failure or aplastic anaemia. This chronic and often severe reduction in RBCs causes typical symptoms such as fatigue, weakness, and shortness of breath. Hence, raising awareness about the condition is crucial as it can help with early diagnosis. About 40 to 50 years ago, the 10-year survival rate for PNH was only around 50%. However, over the past 15 years, advancements in treatment—such as the development of eculizumab—have improved the 10-year survival rate to over 75%.
PNH can lead to life-threatening complications, but treatments are available that can help manage symptoms, reduce the frequency of haemolytic episodes, and lower the risk of blood clots. One of the main treatments involves the use of medications called complement inhibitors, which can help protect RBCs from destruction. In some cases, a bone marrow transplant may be necessary, especially if PNH is accompanied by other bone marrow disorders. Regular monitoring and supportive care are also essential, as they can help manage symptoms and prevent complications. Awareness can thus lead to early detection and improved quality of life.
Hence, do not ignore seemingly normal signs such as extreme fatigue or change in urine colour and do not delay consulting the doctor.
Dr Rayaz Ahmed, Hematologists, Max hospital Saket Delhi
