Pure red cell aplasia is the diagnosis applied to isolated anemia secondary to failure of erythropoiesis. Cardinal findings are a low hemoglobin level combined with reticulocytopenia and absent or extremely infrequent marrow erythroid precursor. Historical names for pure red cell aplasia include erythroblast hypoplasia, erythroblastopenia, red cell agenesis, hypoplastic anemia, and aregenerative anemia. Aplastic anemia confers the same meaning, of course, but is applied to pancytopenia and an empty marrow (Chap. 35). Pure red cell aplasia was first separated from aplastic anemia by Kaznelson in 1922. The association of red cell aplasia and thymoma interested physicians in the 1930s and ultimately led to laboratory studies linking pure red cell aplasia to immune mechanisms, including the early identification of antierythroid precursor cell antibodies by Krantz and later characterization of T cells that inhibited erythropoiesis. Red cell aplasia as an acute and life-threatening complication of sickle cell disease and other hemolytic anemias was recognized in the 1940s, presaging the role of a specific virus in the etiology of both acute and chronic erythropoietic failure. Despite its infrequency, pure red cell aplasia has been a subject of much laboratory research because of its link to an immune mechanism of erythropoietic failure and as a manifestation of parvovirus B19 infection and viral destruction of red cell progenitors. However, because of its infrequency, pure red cell aplasia has not been the subject of large or controlled clinical trials; as a result, therapeutic recommendations are based on single cases or small series. Table 36–1 lists a practical classification of pure red cell aplasia.
Acronyms and Abbreviations:
B19, primate erythroparvovirus 1; BFU-E, burst-forming unit–erythroid; CD20, a cluster of differentiation molecule expressed on the surface of all mature B cells; CFU-E, colony-forming unit–erythroid; CLL, chronic lymphocytic leukemia; FA, Fanconi anemia; GATA1 gene, globin transcription factor 1; HLA, human leukocyte antigen; Ig, immunoglobulin; IL, interleukin; LGL, large granular lymphocytic leukemia; RPS14 and RPS19 genes, ribosomal protein S14 and S19 genes; STAT3 gene, signal transducer and activator of transcription 3 gene; T cell, thymus-derived lymphocyte.
INHERITED PURE RED CELL APLASIA (DIAMOND-BLACKFAN ANEMIA)
Anemia in infancy and early childhood associated with absent reticulocytes in the blood and erythroid precursor cells in the marrow was described by Joseph1 in 1936 as a “failure of erythropoiesis” and by Diamond and Blackfan2 in 1938 as “congenital hypoplastic anemia.” Gasser3 first reported a response of a patient to glucocorticoids in 1951, and Diamond and associates4 presented a series of treated patients. Genetic linkage studies have identified etiologic mutations in ribosomal protein genes.5,6,7,8,9 Hundreds of cases have been reported, and many excellent reviews have been published.10 Although Joseph was the first to describe the disorder, the anemia invariably is referred to as either Blackfan-Diamond or Diamond-Blackfan anemia.