Paroxysmal Nocturnal Hemoglobinuria (PNH)

Paroxysmal nocturnal hemoglobinuria (PNH) is a rare, complex blood disorder caused by damage to the red blood cell membrane, leading to their premature destruction. 

In PNH, the body produces red blood cells that are more vulnerable to destruction by the immune system, resulting in the release of hemoglobin into the blood and urine. 

A characteristic symptom of PNH is hemoglobinuria – the presence of hemoglobin in the urine – which may cause the urine to appear darker, especially in the morning. 

Patients may also experience fatigue, shortness of breath, and abdominal pain. These symptoms stem from anemia (a low red blood cell count), which is a consequence of hemolysis (red blood cells breakdown). 

The disease can be difficult to diagnose because its symptoms are non-specific and may resemble other hematological conditions.

Paroxysmal Nocturnal Hemoglobinuria – Most Common Symptoms

Symptoms of PNH can vary significantly from patient to patient but often include:

• Hemoglobinuria: Dark-colored urine, especially in the morning, due to the presence of free hemoglobin.
• Anemia: Fatigue, weakness, pale skin, and shortness of breath caused by low levels of red blood cells.
• Thrombosis: A tendency to develop blood clots in unusual locations, such as the hepatic veins (hepatic vein thrombosis), abdomen, or brain.
• Abdominal pain: Pain, nausea, and vomiting, which may be related to thrombosis or splenomegaly (enlarged spleen).
• Headaches and dizziness: May be caused by clots or anemia.
• Infections: Increased susceptibility to infections due to damage to white blood cells.
• Kidney dysfunction: Some patients may develop kidney problems as a result of ongoing hemolysis.
• Jaundice or icterus: Yellowing of the skin and eyes due to excess bilirubin, a byproduct of red blood cell breakdown.

Causes of PNH

PNH is caused by a mutation in the PIGA gene, which is essential for the production of certain proteins that protect red blood cells from immune system attacks. This mutation is acquired rather than inherited, meaning it develops during a person’s lifetime and is not present at birth. 

The disease may arise in the context of another condition, such as aplastic anemia, where the bone marrow fails to produce enough blood cells.

Diagnosis of PNH

Diagnosing PNH involves several steps. Initially, a doctor may suspect PNH based on clinical symptoms and medical history. Laboratory tests, such as a complete blood count (CBC), can reveal anemia and other abnormalities. The key diagnostic tool is flow cytometry, which detects the absence of specific proteins on the surface of red blood cells.

Treatment Options

Treatment for PNH focuses on managing symptoms and preventing complications. It includes:

• Treatment of anemia: Blood transfusions may be necessary to maintain adequate red blood cell levels. Iron and folic acid supplementation are also commonly recommended.
• Monoclonal antibodies: These block the C5 protein, preventing red blood cell destruction. This treatment can significantly improve quality of life, although it requires regular intravenous infusions.
• Prevention of blood clots: Anticoagulants, such as warfarin or heparin, may be used to reduce the risk of blood clot formation.
• Bone marrow transplantation: In some cases, particularly when PNH coexists with aplastic anemia, bone marrow transplantation may be considered as a potentially curative option.

Incidence and Prevalence

PNH affects approximately 1 to 1.5 people per million in the population. The disease can occur at any age but most commonly affects young adults. The median age at diagnosis is 35 to 40 years, though it can occasionally be diagnosed in childhood or adolescence.