Introduction

Extract

This focus section includes articles on three anemias associated with bone marrow failure: acquired aplastic anemia (AA), paroxysmal nocturnal hemoglobinuria (PNH), and refractory anemia (RA) and the myelodysplastic syndromes (MDS). These conditions are linked because of similarities in their presentation, laboratory findings, and pathophysiology.^1,2 The association among these diseases began in earnest in 1967, when Lewis and Dacie reported a combined AA-PNH syndrome, and Damashek speculated that a bone marrow insult may be a common factor in the pathophysiology of AA, PNH, and hypoplastic leukemia.^3,4 All three diseases are characterized by cytopenia affecting one or more cell lines. Bone marrow hypocellularity is a characteristic feature of AA, and although not typical, may also be found in MDS and PNH. Reticulocytopenia is characteristically found in AA and MDS, but can also be seen in PNH. This overlap in laboratory findings can cause difficulty in differential diagnosis and classification of these disorders.

A defect in the bone marrow stem cell compartment is another common factor in all three diseases, however different mechanisms are responsible for the cytopenias. In AA, the stem cells are depleted from the marrow by an autoimmune T-cell attack on the stem cell pool.¹ In PNH, a mutation occurs in a stem cell that results in circulating blood cells deficient in glycosylphosphoinositol-linked membrane proteins such as CD55 and CD59. The absence of these surface proteins leads to increased susceptibility to complement-mediated lysis and hemolytic anemia.³ In MDS, clonal mutations in stem cells cause multi-lineage dysplasia and ineffective hematopoiesis.²

The…