Paroxysmal Nocturnal Hemoglobinuria

Larry J Smith

doi:10.29074/ascls.17.3.172

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Larry J Smith, PhD SH(ASCP)⇑
1. is at the Sloan-Kettering Cancer Institute, New York, NY

Address for correspondence: Larry J Smith PhD SH(ASCP), Department of Clinical Laboratories, Memorial Sloan-Kettering Cancer Center, 1275 York Avenue, New York NY 10021. (212) 639-7063. (646) 422-2313 (fax). Smith7{at}mskcc.org

Extract

Paroxysmal nocturnal hemoglobinuria (PNH) is an acquired clonal stem cell disorder resulting from a somatic mutation in the hematopoietic stem cell. It is characterized by intravascular hemolysis, cytopenias, frequent infections, bone marrow hypoplasia, and a high incidence of life-threatening venous thrombosis. An absent glycosylphosphatidylinositol (GPI)-anchored receptor prevents several proteins from binding to the erythrocyte membrane. These include the complement–regulatory proteins, CD55 and CD59, whose absence results in enhanced complement-mediated lysis. Patients present with anemia and hemoglobinuria. Laboratory diagnosis includes the sucrose hemolysis test, Ham acid hemolysis test, and fluorescent-activated cell analysis. There is considerable overlap between PNH, aplastic anemia, and myelodysplastic syndrome and some cases evolve into acute leukemia. Treatment is mainly supportive consisting of trans-fusion therapy, anticoagulation, and antibiotic therapy. Hematopoietic stem cell transplantation may be curative.

Paroxysmal nocturnal hemoglobinuria is an acquired stem cell disorder characterized by intravascular hemolysis, hemoglobinuria, and life-threatening thrombotic episodes.¹ PNH occurs with an incidence of two to six per million persons. In addition, it may be considered a chronic hemolytic anemia caused by a defect intrinsic to the erythrocyte. PNH is unique, in that it is the only hemolytic anemia due to an intrinsic defect that is acquired and not inherited. The disorder was described in 1882 by Strübing as a case of intermittent hemoglobinuria, wherein a patient presented with hemoglobinuria upon awakening.² Strübing went on to suggest that the hemoglobinuria was due to erythrocyte destruction within the blood vessels. Strübing's main contribution was to distinguish his patient from a common condition known…

ABBREVIATIONS: DAF = decay accelerating factor; GPI = glycosylphosphatidylinositol; PNH = paroxysmal nocturnal hemoglobinuria; MIRL = membrane inhibitor of reactive lysis.