Last update:
31-Jul-2015

Paroxysmal nocturnal hemoglobinuria (PNH) or Marchiafava-Micheli disease is an acquired clonal hematopoietic stem cell disorder that few clinicians or even hematologists have followed throughout its full natural history and clinical course. The molecular and biochemical background of PNH was elucidated at the end of the last century following nordecades of research. Over 180 somatic mutations of the X-linked gene PIG-A in hematopoietic stem cells have been implicated in the pathogenesis of PNH, resulting in impairment of the biosynthetic pathway of the glycosyl-phosphatidylinositol (GPI) molecule, which is a glycoprotein mechanism for membrane anchoring. PNH is the first and single example of acquired autoimmune hemolytic anemia with a negative Coombs' test. It is based on a red cell membrane defect with normal morphology, which leads to paroxysmal episodes of hemoglobinuria, with dark-coloured urine most noticeable in the morning. The red cell membrane deficiency of CD55 and CD59, GPI-anchored complement regulatory proteins, adequately explains the symptom of chronic intravascular hemolysis with hemosidirinuria, although the pathogenesis of thromboembolic events in unusual sites and bone marrow failure, which complement the characteristic clinical triad of PNH manifestations, still remains obscure. This review summarizes the available scientific elements of the unique molecular and biochemical defect of PNH and describes the underlying pathogenetic pathways that lead to its clinical manifestations.

Key words: Aplastic anemia, Bone marrow failure, CD55, CD59, Decay accelerating factor, Hemolytic anemia, Membrane inhibitor factor, Paroxysmal nocturnal hemoglobinuria.