Advances in the diagnosis and therapy of paroxysmal nocturnal hemoglobinuria

Research output: Contribution to journalArticle

Abstract

PNH is an uncommon acquired hemolytic anemia that often manifests with hemoglobinuria, abdominal pain, smooth muscle dystonias, fatigue, and thrombosis. The disease results from the expansion of hematopoietic stem cells harboring a mutation in a gene, PIG-A, that is required for the biosynthesis of a lipid moiety, glycosylphosphatidylinositol (GPI), that attaches dozens of different proteins to the cell surface. Thus, PNH cells are deficient in cell surface GPI anchored proteins; this deficiency on erythrocytes leads to intravascular hemolysis since certain GPI anchored proteins normally function as complement regulators. Free hemoglobin released from intravascular hemolysis leads to circulating nitric oxide depletion and is responsible for many of the clinical manifestations of PNH, including fatigue, erectile dysfunction, esophageal spasm, and thrombosis. Interestingly, rare PIG-A mutations can be found in virtually all healthy control subjects leading to speculation that PIG-A mutations in hematopoietic stem cells are common benign events. However, recent data reveals that most of these mutations in healthy controls are not derived from stem cells. The recently FDA approved complement inhibitor eculizumab has been shown to decrease hemolysis, decrease erythrocyte transfusion requirements, decrease the risk for thrombosis and improve quality of life for PNH patients.

Original languageEnglish (US)
Pages (from-to)65-74
Number of pages10
JournalBlood Reviews
Volume22
Issue number2
DOIs
StatePublished - Mar 2008

Fingerprint

Paroxysmal Hemoglobinuria
Glycosylphosphatidylinositols
Hemolysis
Mutation
Thrombosis
Complement Inactivating Agents
Hematopoietic Stem Cells
Diffuse Esophageal Spasm
Hemoglobinuria
Erythrocyte Transfusion
Muscle Fatigue
Dystonia
Hemolytic Anemia
Erectile Dysfunction
Therapeutics
Abdominal Pain
Fatigue
Smooth Muscle
Healthy Volunteers
Nitric Oxide

Keywords

  • Complement
  • Eculizumab
  • FLAER
  • Glycosylphosphatidylinositol anchored protein
  • Nitric oxide
  • Paroxysmal nocturnal hemoglobinuria
  • PIG-A
  • Proaerolysin

ASJC Scopus subject areas

  • Cancer Research
  • Hematology
  • Oncology

Cite this

Advances in the diagnosis and therapy of paroxysmal nocturnal hemoglobinuria. / Brodsky, Robert A.

In: Blood Reviews, Vol. 22, No. 2, 03.2008, p. 65-74.

Research output: Contribution to journalArticle

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