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Pathophysiology of PNH
PNH: A Hematopoietic Stem Cell Disorder
PNH is an acquired hematopoietic stem cell disorder in which blood cells lack key, naturally occurring terminal complement inhibitors on the cell surface, rendering them vulnerable to lysis by the terminal complement complex (TCC), also known as C5b-9 or the membrane attack complex (MAC).1-3
PNH results from the expansion of hematopoietic stem cells that possess a mutation of the phosphatidylinositol glycan class A (PIG-A) gene. This mutation results in a deletion of GPI anchors, which normally tether certain types of proteins to the cell surface. These proteins are unable to attach to the surface of the cell in PNH.1,2
PNH cells are frequently found in patients with other hematological conditions, including aplastic anemia (AA), myelodysplastic syndromes (MDS), and other forms of bone marrow failure.4
Patients with conditions such as Coombs-negative hemolytic anemia, hemoglobinuria, aplastic anemia (AA), myelodysplastic syndromes (MDS) such as refractory anemia-MDS (RA-MDS), unexplained cytopenias, and unexplained thrombosis are at higher risk for PNH than the general population.5-8
1. Rosse WF, Hillmen P, Schreiber AD. Hematology (Am Soc Hematol Educ Program). 2004:48-62.
2. Wiedmer T, Hall SE, Ortel TL, Kane WH, Rosse WF, Sims PJ. Blood. 1993;82:1192-1196. 3. Rother RP, Bell L, Hillmen P, Gladwin MT. JAMA. 2005;293:1653-1662. 4. Parker C, Omine M, Richards S, et al, for the International PNH Interest Group. Blood. 2005;106:3699-3709. 5.Hillmen P, Lewis SM, Bessler M, Luzzatto L, Dacie JV. N Engl J Med. 1995;333:1253-1258. 6. Borowitz MJ, Craig FE, DiGiuseppe JA, et al; for Clinical Cytometry Society. Cytometry Part B Clin Cytom. doi:10.1002/cyto.b.20525. 7. Galili N, Ravandi F, Palermo G, et al. 2009 American Society of Clinical Oncology Annual Meeting; May 30, 2009; Orlando, FL. 8. Myelodysplastic syndromes. NCCN Clinical Practice Guidelines in Oncology. Version 2; 2010. National Comprehensive Cancer Network.
2. Wiedmer T, Hall SE, Ortel TL, Kane WH, Rosse WF, Sims PJ. Blood. 1993;82:1192-1196. 3. Rother RP, Bell L, Hillmen P, Gladwin MT. JAMA. 2005;293:1653-1662. 4. Parker C, Omine M, Richards S, et al, for the International PNH Interest Group. Blood. 2005;106:3699-3709. 5.Hillmen P, Lewis SM, Bessler M, Luzzatto L, Dacie JV. N Engl J Med. 1995;333:1253-1258. 6. Borowitz MJ, Craig FE, DiGiuseppe JA, et al; for Clinical Cytometry Society. Cytometry Part B Clin Cytom. doi:10.1002/cyto.b.20525. 7. Galili N, Ravandi F, Palermo G, et al. 2009 American Society of Clinical Oncology Annual Meeting; May 30, 2009; Orlando, FL. 8. Myelodysplastic syndromes. NCCN Clinical Practice Guidelines in Oncology. Version 2; 2010. National Comprehensive Cancer Network.
Dr Wendell Rosse explains how PNH is not paroxysmal, not nocturnal, and usually doesn’t involve hemoglobinuria at presentation.
Dr Wendell Rosse explains how the pathophysiology of PNH can lead to thrombosis.