Paroxysmal nocturnal hemoglobinuria (membrane defect, pathogenesis, aplastic anemia, diagnosis).
Paroxysmal nocturnal hemoglobinuria (PNH) is an acquired clonal disorder in which intravascular hemolysis results from the somatic mutation of the totipotent stem cells causing an intrinsic defect in red cell membrane. PNH cells lack glycosylphosphatidylinositol (GPI) anchored membrane proteins. Of these proteins absence of CD 59 (MIRL--membrane inhibitor of reactive lysis, protectin) and CD 55 (DAF--decay accelerating factor) makes the PNH cells abnormally sensitive to the lytic action of complement. The defect appears to be in the somatic mutation of the X-linked PIG-A (phosphatidylinositolglycan A class) gene which participate in an early step of GPI-anchor synthesis. PNH is characterized by recurrent life threatening venous thromboses and an intimate association with aplastic anemia (AA). It seems that PNH always coexists with bone marrow failure (BMF) (37). The possible explanation may be that some GPI-anchored proteins may be a critical target recognized by immune effector cells. PNH clones not possessing these critical GPI-anchored proteins will survive because they are selectively resistant to the autoimmune assault that eliminates most normal clones. The flow cytometry of erythrocytes using anti-CD 59 and anti-CD 59 and anti-CD 55 of granulocytes has been now introduced as a very sensitive and quantitative method of PNH diagnosis able to detect PNH cells even in normal individuals (1,54). Thus it seems now clear that we must make distinction between the detection of very occasional PNH cells in patients with BMF and PNH as a clinicohematological entity. Unfortunately, we do not know the minimal content of PNH cells required to produce clinical signs of PNH (38).
Chrobák
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Department of Clinical Hematology, University Teaching Hospital, Hradec Králové.
D000741:Anemia, Aplastic / Q000150:complications; D004910:Erythrocyte Membrane / Q000378:metabolism; D006457:Hemoglobinuria, Paroxysmal / Q000150:complications / Q000175:diagnosis / Q000503:physiopathology / Q000628:therapy; D006801:Humans; D008565:Membrane Proteins / Q000378:metabolism; D013927:Thrombosis / Q000150:complications
D008565:Membrane Proteins