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Pure Red Cell Aplasia

Clinical features of pure red cell aplasia include anemia, reticulocytopenia, and an absence or paucity of recognizable red cell precursors in marrow. Cytogenetic studies normal but 5q- myelodysplasia syndrome often a chronic aregenerative anemia. Major differential with constitutional red cell aplasia (Diamond-Blackfan syndrome) and persistent parvovirus infection.

Associations and pathophysiology. Some cases resemble an immune disease (associated thymoma) or deficient immunoglobulins, and others like acquired genetic disorders (5q- syndrome). Can occur secondary to drugs.

Immune pathophysiology. Association with thymoma probably exaggerated, and a thymic tumor present in only about 10% of patients. Look for mediastinal mass because tumor may be malignant. Other associated autoimmune syndromes like systemic lupus, myasthenia gravis, abnormalities of immunoglobulin quantity. Pure red cell aplasia relatively frequent in chronic lymphocytic leukemia. Drug-dependent red cell aplasia with diphenylhydantoin.

Immune pathogenesis an antibody to erythroid precursor cells in some patients. Cytotoxic T cells in a large proportion.

Parvovirus infection. BI9 parvovirus cause of fifth disease in normal individuals and transient aplastic crisis in underlying hemolysis. Virus directly infects and lyses erythroid progenitor cells. Virus infection ordinarily terminated by production of neutralizing antibodies; if no antibodies.

Therapy. About two-thirds of patients with pure red cell aplasia respond to some form of immunosuppression: steroids, azathioprine, cyclophosphamide, and 6-mercaptopurine first line; also ATG and cyclosporine. Thymectomy usually not helpful for anemia. Hematopoietic colony cultures predictive of response to immunosuppressive treatment.

Clinical features. Pancytopenia of the peripheral blood with bone marrow hypocellularity. Usually presents with bleeding, especially in skin and mucous membranes, or complaints due to anemia. Mortality secondary to infection, especially fungi like Aspergillosis.

Survival a function of blood counts. Severe disease defined by satisfaction of 2 of 3 peripheral blood criteria: 1. absolute neutrophil count <500/:L, 2. platelets <20,000/:L, and 3. reticulocytes <1%. Neutrophils <200/:L defines "super-severe" category. High mortality of "untreated" severe aplastic anemia: <10-20% survival at one year with transfusions only.

Differential diagnosis. In secondary cases underlying illness usually obvious from history and physical examination. Distinguish especially:

Constitutional aplastic anemia (Fanconi's anemia) in adults.

Myelodysplasia may be hypocellular in about 20% of cases.

Chromosomal analysis of bone marrow cells is almost always normal in aplastic anemia, myelodysplasia is associated with the 5q- deletion and other cytogenetic abnormalities. There are patients in whom the distinction between MDS and AA is so difficult.