Paroxysmal nocturnal hemoglobinuria pathophysiology
Paroxysmal nocturnal hemoglobinuria Microchapters |
Differentiating Paroxysmal nocturnal hemoglobinuria from other Diseases |
---|
Diagnosis |
Treatment |
Case Studies |
Paroxysmal nocturnal hemoglobinuria pathophysiology On the Web |
American Roentgen Ray Society Images of Paroxysmal nocturnal hemoglobinuria pathophysiology |
Paroxysmal nocturnal hemoglobinuria pathophysiology in the news |
Blogs on Paroxysmal nocturnal hemoglobinuria pathophysiology |
Directions to Hospitals Treating Paroxysmal nocturnal hemoglobinuria |
Risk calculators and risk factors for Paroxysmal nocturnal hemoglobinuria pathophysiology |
Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief:
Overview
Pathophysiology
Physiology
- Normally, Red Blood Cells (RBCs), alike other cells in the body, have surface proteins that acts as a communicating signal between the cells and the environment.
- The signaling proteins are most commonly attached to the surface of the RBCs by glycolipids. The most common glycolipid is the glycosyl phosphatidylinositols (GPI).
- The attached proteins are also protective to the cells against destruction by the complement system.[1]
- The RBCs are mainly protected by proteins called decay accelerating factor (DAF/CD55). The DAF or CD55 proteins prevent the formation of C3-convertase enzyme, the protectin (CD59), and the C9 which are components of the complement inflammatory system.[2]
Pathogenesis
- It is understood that paroxysmal nocturnal hemoglobinuria is caused by genetic mutation and complement mediated hemolysis.
PIGA gene mutation and PNH
- The acquired gene mutation of PIGA gene (Posphatidylinositol Glycan anchor biosynthesis, class A) is the main pathogenic factor in developing PNH. The PIGA gene is responible for the GPI anchor synthesis.
- The PIGA gene is found on the X chromosome and that concludes the affection of all males who have the mutation in one allele. However, the females will be carrier if one allele affected and a second genetic "hit" must take place to develop the disease.
- The PIGA gene mutation is most common a frame shift mutation which results in a misfolded protein product which is nonfunctional proteins and degraded by proteasomes.
- It is believed the mutation mechanism is caused by exposure to radiation, chemotherapy, or DNA repair defects.
- Other mutations:
- Lack of the CD59 on the RBCs surface membrane is strongly related to the clinical signs of PNH. It is related to the intravascular hemolysis and peripheral neuropathy.
Genetics
Genes involved in the pathogenesis of paroxysmal nocturnal hemoglobinuria include:[3]
- PIGA gene
- TET2
- SUZ12
- U2AF1
- JAK2
Associated Conditions
- However, paroxysmal nocturnal hemoglobinuria is usually associated with the following diseases:[4]
- Aplastic anemia
- Myelodysplastic anemia
- Acute myelogenous anemia
Microscopic Pathology
On microscopic histopathological analysis, [feature1], [feature2], and [feature3] are characteristic findings of [disease name].
References
- ↑ Parker C, Omine M, Richards S, Nishimura J, Bessler M, Ware R; et al. (2005). "Diagnosis and management of paroxysmal nocturnal hemoglobinuria". Blood. 106 (12): 3699–709. doi:10.1182/blood-2005-04-1717. PMC 1895106. PMID 16051736.
- ↑ Parker C, Omine M, Richards S, Nishimura J, Bessler M, Ware R; et al. (2005). "Diagnosis and management of paroxysmal nocturnal hemoglobinuria". Blood. 106 (12): 3699–709. doi:10.1182/blood-2005-04-1717. PMC 1895106. PMID 16051736.
- ↑ Shen W, Clemente MJ, Hosono N, Yoshida K, Przychodzen B, Yoshizato T; et al. (2014). "Deep sequencing reveals stepwise mutation acquisition in paroxysmal nocturnal hemoglobinuria". J Clin Invest. 124 (10): 4529–38. doi:10.1172/JCI74747. PMC 4191017. PMID 25244093.
- ↑ Brodsky RA (2014). "Paroxysmal nocturnal hemoglobinuria". Blood. 124 (18): 2804–11. doi:10.1182/blood-2014-02-522128. PMC 4215311. PMID 25237200.