- Paroxysmal Nocturnal Hemoglobinuria (PNH) is a rare acquired blood disorder characterized by the destruction of red blood cells (hemolysis), blood clots (thrombosis), and impaired bone marrow function. The condition occurs due to a genetic mutation in the PIGA gene in blood-forming stem cells, which leads to the production of blood cells that lack certain protective proteins on their surface, making them vulnerable to attack by the body’s complement system.
- The name of the condition is somewhat misleading, as hemolysis can occur at any time of day, not just at night, and many patients may not experience noticeable color changes in their urine. The condition develops when a mutation occurs in a small number of blood-forming stem cells in the bone marrow. These mutated cells produce blood cells that lack glycosylphosphatidylinositol (GPI) anchor proteins, which normally protect cells from destruction by the complement system, a part of the body’s natural immune defense.
- The primary symptoms of PNH can vary significantly among patients but often include fatigue, shortness of breath, and dark-colored urine (due to the presence of hemoglobin). Other common symptoms include chest pain, abdominal pain, difficulty swallowing, erectile dysfunction, and headaches. Many of these symptoms are related to both the destruction of red blood cells and the formation of blood clots in unusual locations, such as the abdominal and cerebral veins.
- One of the most serious complications of PNH is thrombosis, which can occur in unusual sites such as the hepatic and cerebral veins. These blood clots can be life-threatening and are a major cause of mortality in PNH patients. Additionally, patients may develop bone marrow failure, leading to decreased production of all blood cell types (pancytopenia), which can cause increased risk of infection and bleeding.
- Diagnosis of PNH typically involves flow cytometry testing of blood cells to detect the absence of GPI-anchored proteins. This test can determine the percentage of blood cells affected by the PNH mutation, which helps guide treatment decisions. Other tests may include complete blood count, reticulocyte count, lactate dehydrogenase levels, and various clotting studies.
- Treatment of PNH has been revolutionized by the development of complement inhibitor therapy, particularly eculizumab and ravulizumab. These medications block the complement system’s attack on red blood cells, effectively preventing hemolysis and reducing the risk of thrombosis. Some patients may also require supportive care such as blood transfusions, iron supplementation, and anticoagulation therapy to prevent blood clots.
- The prognosis for PNH patients has improved dramatically with modern treatments. Before the advent of complement inhibitor therapy, the median survival was approximately 10-15 years from diagnosis. However, with current treatments, many patients can live normal lifespans with good quality of life. Regular monitoring is essential to adjust treatment as needed and watch for complications.
- Patients with PNH require comprehensive care from a specialized medical team, typically including hematologists and other specialists. Management often involves regular blood tests to monitor disease activity, vaccination against certain infections (particularly meningococcal infections, due to the increased risk while on complement inhibitor therapy), and careful attention to symptoms that might indicate thrombosis or other complications.
- Research continues in the field of PNH, with new treatments under development and investigation into potential curative approaches. The only current cure for PNH is allogeneic bone marrow transplantation, but this procedure carries significant risks and is typically reserved for patients with severe bone marrow failure or those who don’t respond well to other treatments.
