Update on the diagnosis and management of paroxysmal nocturnal hemoglobinuria

Abstract

Once suspected, the diagnosis of paroxysmal nocturnal hemoglobinuria (PNH) is straightforward when flow cytometric analysis of the peripheral blood reveals a population of glycosyl phosphatidylinositol anchor protein-deficient cells. But PNH is clinically heterogeneous, with some patients having a disease process characterized by florid intravascular, complement-mediated hemolysis, whereas in others, bone marrow failure dominates the clinical picture with modest or even no evidence of hemolysis observed. The clinical heterogeneity is due to the close, though incompletely understood, relationship between PNH and immune-mediated bone marrow failure, and that PNH is an acquired, nonmalignant clonal disease of the hematopoietic stem cells. Bone marrow failure complicates management of PNH because compromised erythropoiesis contributes, to a greater or lesser degree, to the anemia; in addition, the extent to which the mutant stem cell clone expands in an individual patient determines the magnitude of the hemolytic component of the disease. An understanding of the unique pathobiology of PNH in relationship both to complement physiology and immune-mediated bone marrow failure provides the basis for a systematic approach to management.

Paroxysmal nocturnal hemoglobinuria (PNH): An atypical case report

“…This mutation is located on X chromosome at the level of phosphatidyl-inositol glycan (GPI) class A gene. [2][3][4][5][6] This gene is required for GPI synthesis, a glycolipid derivative necessary to anchor number of proteins to cell surface. [3][4][5] Thus descending cells from affected stem cells (erythrocytes, granulocytes, platelets, monocytes and lymphocytes) will be deficient for all GPI-anchored proteins.…”

“…[3][4][5] Thus descending cells from affected stem cells (erythrocytes, granulocytes, platelets, monocytes and lymphocytes) will be deficient for all GPI-anchored proteins. [2][3][4][5][6] Among twenty deficient proteins, DAF (decay accelerating factor) or CD 55 and MIRL (membrane inhibitor of reactive lysis) or CD 59, both primary regulators of complement at the level of erythrocyte membrane will be of peculiar interest. [2][3][4][5][6] In fact their lowering will refer to intravascular complement mediated hemolysis, one of the 3 key symptoms of the disease.…”

“…[2][3][4][5][6] Among twenty deficient proteins, DAF (decay accelerating factor) or CD 55 and MIRL (membrane inhibitor of reactive lysis) or CD 59, both primary regulators of complement at the level of erythrocyte membrane will be of peculiar interest. [2][3][4][5][6] In fact their lowering will refer to intravascular complement mediated hemolysis, one of the 3 key symptoms of the disease. [2][3][4][5][6] Effectively the frequency of hemolytic crises is in direct relation to PGI clone size and LDH serum levels.…”

“…Recent studies have shown that the disease was related to an acquired mutation of hematopoietic stem cell on phosphatidyl-inositol glycan (GPI) class A (PIG-A) gene located on X chromosome. [2][3][4][5][6] This mutation will lead to a partial or complete failure of proteins linked to cell membrane through a glycophosphatidylinositol (GPI) anchor. [2][3][4][5][6] We report the case of a young woman whose initial presentation was atypical.…”

“…The diagnosis of PNH was confirmed by flow cytometry determinations of specific PNH markers CD55, CD59 and aerolysin. [2][3][4][5][6] A small GPI-deficient clone of 7% in circulating blood and 19% on medullary cells was notified. Considering the importance of bone marrow failure, the therapeutic choice was oriented towards an allogenic bone marrow grafting.…”