Paroxysmal Nocturnal Hemoglobinuria (PNH) Profile (LAB928)

Paroxysmal nocturnal hemoglobinuria (PNH) is a rare hematopoietic disorder characterized by complement-mediated lysis of blood lineage cells due to somatic mutation(s) in the PIGA gene, leading to a lack of glycosyl-phosphatidyl inositol (GPI)-linked proteins on the cell surface. Flow cytometric analysis is considered the gold standard for PNH detection and monitoring due to its increased sensitivity and specificity compared to other tests.

• Older tests for PNH, such as the Ham test or sucrose hemolysis, lack the sensitivity and specificity of flow cytometry and are no longer commonly used.

• Flow cytometric analysis is the preferred method for PNH detection and monitoring, performed with antibodies directed at GPI-linked cell surface proteins and a fluorescently labeled inactive bacterial toxin aerolysin (FLAER) protein that directly binds GPI molecules.
• Loss of expression of GPI-linked cell surface proteins and GPI linker molecules should be identified in at least two hematopoietic cell lineages for a diagnosis of PNH; the most frequently assessed lineages are erythroid (red blood cells) and myeloid (neutrophils, monocytes) lineages.

1. Brodsky RA. Paroxysmal nocturnal hemoglobinuria. In: Hoffman R, Benz EJ Jr, Silberstein LE, Heslop HE, Weitz JI, Anastasi J, eds. Hematology: Basic Principles and Practice. 7th ed. Philadelphia, PA: Elsevier; 2018:chap 29.
2. Hillmen P, Lewis SM, Bessler M, Luzzatto L, Dacie JV. Natural history of paroxysmal nocturnal hemoglobinuria. N Engl J Med. 1995 Nov 9;333(19):1253-8. doi: 10.1056/NEJM199511093331903. PMID: 7565977.