Last update:

   07-Dec-2015
 

Arch Hellen Med, 32(6), November-December 2015, 679-700

REVIEW

The pathophysiological mechanisms of the pathogenesis of bone marrow failure
in paroxysmal nocturnal hemoglobinuria, and new insights

J.V. Asimakopoulos,1 O. Kampouropoulou,2 L. Papageorgiou,1 M. Samarkos,2 E. Variami,2 T.P. Vassilakopoulos,1
M.K. Angelopoulou,1 P. Tsaftaridis,1 E. Plata,1 E. Terpos,3 K. Konstantopoulos,1 J. Meletis1

1Department of Hematology and Bone Marrow Transplantation Unit, National and Kapodistrian University of Athens, School of Medicine, "Laiko" General Hospital, Athens,
2First Department of Internal Medicine, National and Kapodistrian University of Athens, School of Medicine, "Laiko" General Hospital, Athens,
3Department of Clinical Therapeutics, National and Kapodistrian University of Athens, School of Medicine, "Alexandra" General Hospital, Athens, Greece

Paroxysmal nocturnal hemoglobinuria (PNH), or Marchiafava-Micheli disease, is the first and only 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, most noticeable in the morning. The redcell membrane deficiency of CD55 and CD59, glycosyl-phosphatidyl-inositol (GPI)-anchored complement regulatory proteins, explains adequately the symptom of chronic intravascular hemolysis with hemosidirinuria. Recent data have demonstrated the importance of GPI-anchored membrane proteins deficiency in the pathogenesis of thromboembolic events in unusual sites that characterize the clinical course and natural history of the disease. PNH, however, includes an extremely rare acquired clonal hematopoietic stem cell disorder, a benign oligoclonal myelopathy ubiquitous to varying degrees in all cases of PNH, which cannot be explained simply by somatic mutation of the Xlinked gene PIG-A and the impaired biosynthesis GPI anchor. Thus, the eti╬┐logy of bone marrow failure, which complements the characteristic clinical triad of PNH manifestations, still remains obscure. This review summarizes the currently available scientific data concerning the pathophysiological pathways involved in the bone marrow failure of PNH, and describes a hypothetical pathogenetic model for the disease.

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


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