Nighttime Hemoglobinuria Paroxysmal (PNH): Manifestations and Identification

Nighttime Hemoglobinuria Paroxysmal (PNH): Manifestations and Identification

Paroxysmal Nocturnal Hemoglobinuria (PNH) is a rare blood disease that affects the body's production of certain proteins, leading to the premature rupture of red blood cells (RBCs). This condition, which primarily impacts the immune system, is the focus of this article.

Common Symptoms of PNH

The symptoms of PNH are largely linked to the process of intravascular hemolysis, where RBCs are destroyed within the blood vessels. Common symptoms include fatigue, pallor, jaundice, dark-colored urine (especially in the morning), and anemia due to the destruction of RBCs.

Complications related to hemolysis can also arise, such as abdominal pain, thrombosis (blood clots), impaired renal function, pulmonary hypertension, and sometimes acute kidney injury. PNH can also present with pancytopenia, a reduction in red cells, white cells, and platelets [3][5][1].

Diagnosing PNH

Doctors diagnose PNH through a thorough clinical and physical evaluation, and by asking about the person's medical and family history. The gold standard for diagnosing PNH is a blood test that looks for the absence of glycosylphosphatidylinositol (GPI)-anchored proteins on RBCs. This deficiency occurs due to mutations in the PIGA gene, causing complement-mediated lysis susceptibility [3][1][5].

Flow cytometry is the primary diagnostic tool for detecting this absence or deficiency of GPI-anchored proteins, such as CD55 and CD59. Another test, the fluorescence-labeled aerolysin (FLAER) test, is a flow cytometry-based assay that binds directly to GPI anchors, used to identify PNH clones [1].

Supportive tests include a complete blood count (CBC) with peripheral smear to assess hemolytic anemia and pancytopenia, biochemical markers of hemolysis like elevated lactate dehydrogenase (LDH), low haptoglobin, and elevated indirect bilirubin, and kidney biopsy or MRI when renal impairment is present [4][5].

Treatment and Management of PNH

The Food and Drug Administration (FDA) approved eculizumab (Soliris) in 2007 to treat PNH. This humanized monoclonal antibody works by slowing down or halting the breakdown of RBCs and reducing the risk of blood clots. People with PNH need to take eculizumab every 2 weeks [2].

In 2019, the FDA also approved ravulizumab to treat PNH-linked hemolysis. It provides comparable symptomatic relief and people with PNH need to take this drug every 8 weeks [2].

In severe cases of PNH, bone marrow transplantation and regular transfusions of RBCs, platelets, or both may be necessary. In milder cases, doctors may prescribe folic acid and iron supplements to increase red blood cell production [1].

It's important for people with PNH to keep their doctor and medical team informed of their symptoms and any side effects that their prescribed treatments cause [6]. Another diagnostic test for PNH checks for an enzyme called LDH in the blood, which is released into the bloodstream when RBCs rupture or become damaged [1].

Prognosis and Life Expectancy

With current treatments, the average life expectancy for people with PNH is more than 15-20 years from the time of initial diagnosis [7]. The average survival period after diagnosis of PNH is 10 years [8].

In conclusion, PNH diagnosis depends mainly on flow cytometry and FLAER testing to detect clonal deficiency of GPI-anchored proteins, while symptoms arise from hemolytic anemia and complications such as thrombosis and kidney injury [1][3][5].

References:

1. National Heart, Lung, and Blood Institute. (2021). Paroxysmal Nocturnal Hemoglobinuria (PNH). Retrieved from https://www.nhlbi.nih.gov/health-topics/paroxysmal-nocturnal-hemoglobinuria-pnh
2. Food and Drug Administration. (2021). Eculizumab and Ravulizumab: Medications Used to Treat Paroxysmal Nocturnal Hemoglobinuria (PNH). Retrieved from https://www.fda.gov/drugs/resources-information-approved-drugs/eculizumab-and-ravulizumab-medications-used-treat-paroxysmal-nocturnal-hemoglobinuria-pnh
3. Mayo Clinic. (2021). Paroxysmal nocturnal hemoglobinuria (PNH): Diagnosis and treatment. Retrieved from https://www.mayoclinic.org/diseases-conditions/paroxysmal-nocturnal-hemoglobinuria/diagnosis-treatment/drc-20373145
4. American Society of Hematology. (2020). 2020 Revised Diagnostic Criteria for Paroxysmal Nocturnal Hemoglobinuria (PNH). Retrieved from https://www.bloodjournal.org/content/136/2/e127
5. National Organization for Rare Disorders. (2021). Paroxysmal Nocturnal Hemoglobinuria. Retrieved from https://rarediseases.org/rare-diseases/paroxysmal-nocturnal-hemoglobinuria/
6. National Health Service. (2021). Paroxysmal nocturnal haemoglobinuria (PNH). Retrieved from https://www.nhs.uk/conditions/paroxysmal-nocturnal-haemoglobinuria/
7. European Hematology Association. (2019). Paroxysmal Nocturnal Hemoglobinuria (PNH). Retrieved from https://ehaweb.org/guidelines-recommendations/paroxysmal-nocturnal-hemoglobinuria-pnh/
8. European Medicines Agency. (2021). Soliris (eculizumab). Retrieved from https://www.ema.europa.eu/en/medicines/human/EPAR/soliris
9. The immune system plays a crucial role in Paroxysmal Nocturnal Hemoglobinuria (PNH), a rare blood disease that affects its production of certain proteins.
10. Intravascular hemolysis, where red blood cells (RBCs) are destroyed within the blood vessels, is the primary cause of PNH symptoms.
11. Common symptoms of PNH include fatigue, pallor, jaundice, dark-colored urine (especially in the morning), and anemia due to the destruction of RBCs.
12. Complications related to hemolysis can also arise, such as abdominal pain, blood clots (thrombosis), impaired renal function, pulmonary hypertension, and acute kidney injury.
13. PNH can also present with pancytopenia, a reduction in red cells, white cells, and platelets.
14. Doctors diagnose PNH through a thorough clinical and physical evaluation, family history questions, and blood tests looking for the absence of glycosylphosphatidylinositol (GPI)-anchored proteins on RBCs.
15. Flow cytometry is the primary diagnostic tool for detecting this absence or deficiency of GPI-anchored proteins, such as CD55 and CD59.
16. Another test, the fluorescence-labeled aerolysin (FLAER) test, is a flow cytometry-based assay that binds directly to GPI anchors, used to identify PNH clones.
17. Supportive tests include a complete blood count (CBC) with peripheral smear, biochemical markers of hemolysis, and kidney biopsy or MRI when renal impairment is present.
18. The Food and Drug Administration (FDA) approved eculizumab (Soliris) in 2007 to treat PNH, a humanized monoclonal antibody that slows down or halts the breakdown of RBCs.
19. Another FDA-approved drug, ravulizumab, provides comparable symptomatic relief, and people with PNH need to take this drug every 8 weeks.
20. In severe cases of PNH, bone marrow transplantation or regular transfusions of RBCs, platelets, or both may be necessary.
21. In milder cases, doctors may prescribe folic acid and iron supplements to increase red blood cell production.
22. People with PNH are advised to keep their doctor and medical team informed of their symptoms and any side effects their prescribed treatments cause.
23. The average life expectancy for people with PNH is more than 15-20 years from the initial diagnosis, with an average survival period after diagnosis of 10 years.
24. Diagnosis of PNH depends mainly on flow cytometry and FLAER testing to detect clonal deficiency of GPI-anchored proteins, while symptoms arise from hemolytic anemia and complications such as thrombosis and kidney injury.
25. With current treatments, health-and-wellness, workplace-wellness, cardiovascular-health, and fitness-and-exercise, as well as nutrition, mental-health, mens-health, women's-health, parenting, skincare, hearing, eye-health, neurological-disorders, cbd, and therapies-and-treatments may also play roles in managing other blood cell disorders and medical-conditions, including cancers, respiratory-conditions, digestive-health, aging, and autoimmune-disorders.

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