Summary about Disease
Paroxysmal nocturnal hemoglobinuria (PNH) is a rare, acquired (not inherited) life-threatening disease of the blood. It's characterized by the destruction of red blood cells (hemolysis), blood clots (thrombosis), and impaired bone marrow function. The name comes from the observation that some patients pass dark urine, especially in the morning, due to the release of hemoglobin into the urine overnight. However, not all patients experience this. PNH arises from a genetic mutation in bone marrow cells that leads to a deficiency of certain protective proteins on the surface of blood cells. This makes the cells susceptible to destruction by the complement system, a part of the immune system.
Symptoms
Symptoms of PNH can vary widely in severity and can include:
Fatigue
Shortness of breath
Dark-colored urine (often first thing in the morning)
Anemia (low red blood cell count)
Blood clots (thrombosis), which can occur in unusual locations like abdominal veins
Abdominal pain
Difficulty swallowing (dysphagia)
Erectile dysfunction (in men)
Bone pain
Jaundice (yellowing of the skin and eyes)
Causes
PNH is caused by an acquired (not inherited) mutation in the PIGA gene in a hematopoietic stem cell (a blood-forming cell) in the bone marrow. This mutation leads to a deficiency of glycosylphosphatidylinositol (GPI), a molecule that anchors certain proteins to the surface of blood cells. Two important proteins anchored by GPI are CD55 and CD59, which protect blood cells from destruction by the complement system. Without these proteins, the complement system attacks and destroys the red blood cells, white blood cells, and platelets.
Medicine Used
Eculizumab (Soliris) and Ravulizumab (Ultomiris): These are complement inhibitors that block the part of the immune system that destroys blood cells in PNH. They are the primary treatment for PNH and can significantly reduce hemolysis, thrombosis, and the need for transfusions.
Pegcetacoplan (Empaveli): Another complement inhibitor that works differently than eculizumab and ravulizumab.
Iron Supplements: To treat iron deficiency resulting from chronic blood loss.
Folic Acid Supplements: To help with red blood cell production.
Blood Transfusions: To treat severe anemia.
Bone Marrow Transplant (Hematopoietic Stem Cell Transplant): In rare and severe cases, a bone marrow transplant may be considered as a curative option.
Anticoagulants: To prevent or treat blood clots.
Is Communicable
No, PNH is not communicable. It is not contagious and cannot be spread from person to person. It's caused by a genetic mutation within the individual's own bone marrow cells.
Precautions
Precautions for individuals with PNH focus on managing the disease and preventing complications:
Adherence to Medication: Strictly follow the prescribed medication regimen, especially complement inhibitors.
Vaccinations: Stay up-to-date on vaccinations, especially against encapsulated bacteria like Neisseria meningitidis (meningococcus), as complement inhibitors increase the risk of infection.
Blood Clot Prevention: Be aware of the signs and symptoms of blood clots and seek immediate medical attention if they occur. Discuss anticoagulant therapy with your doctor if appropriate.
Infection Prevention: Practice good hygiene to minimize the risk of infections.
Avoid Iron Overload: Monitor iron levels and avoid excessive iron supplementation, as it can lead to complications.
Regular Monitoring: Undergo regular blood tests and checkups to monitor disease activity and treatment effectiveness.
How long does an outbreak last?
PNH is a chronic condition, not an "outbreak." It's a long-term disease that requires ongoing management. The symptoms can fluctuate in intensity, with periods of increased hemolysis and thrombosis (sometimes referred to as crises). Without treatment, the disease persists indefinitely. The duration of symptomatic periods or crises varies from person to person and can last for days, weeks, or even months. With effective treatment (complement inhibitors), the symptoms can be well controlled, and the disease course can be significantly improved.
How is it diagnosed?
PNH is diagnosed through specialized blood tests:
Flow Cytometry: This is the primary diagnostic test. It detects the absence of GPI-anchored proteins (CD55 and CD59) on the surface of blood cells (red blood cells, white blood cells). It's highly sensitive and specific.
Complete Blood Count (CBC): To assess red blood cell count, white blood cell count, and platelet count.
Lactate Dehydrogenase (LDH): Elevated levels indicate red blood cell destruction (hemolysis).
Reticulocyte Count: Measures the number of young red blood cells, which may be elevated due to increased red blood cell production in response to hemolysis.
Direct Antiglobulin Test (DAT or Coombs Test): This test is usually negative in PNH, which helps differentiate it from other hemolytic anemias.
Bone Marrow Biopsy (Optional): May be performed to rule out other bone marrow disorders.
Timeline of Symptoms
The onset of symptoms can be gradual or sudden. There is no one set timeline as symptoms vary person to person.
Early Stages: May include subtle symptoms like fatigue, mild anemia, and occasional dark urine. Some people may be asymptomatic initially.
Progression: As the disease progresses, symptoms become more pronounced. Anemia worsens, leading to more severe fatigue, shortness of breath, and chest pain. Hemoglobinuria becomes more frequent and noticeable. Blood clots may occur.
Complications: Over time, complications like kidney damage, pulmonary hypertension, and organ damage due to thrombosis can develop.
With Treatment: With complement inhibitors, symptoms can be significantly reduced or eliminated. However, treatment is lifelong and requires ongoing monitoring.
Important Considerations
Pregnancy: PNH can pose risks during pregnancy. Close monitoring and management are essential.
Surgery: Patients with PNH require careful management before, during, and after surgery to minimize the risk of blood clots and other complications.
Other Medical Conditions: PNH can be associated with other bone marrow disorders like aplastic anemia and myelodysplastic syndromes.
Psychological Impact: Living with a chronic and potentially life-threatening disease can have a significant psychological impact. Support groups and counseling can be helpful.
Lifelong Management: PNH requires lifelong monitoring and treatment. Adherence to medication and regular follow-up with a hematologist are crucial.