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INTRODUCTION

SUMMARY

Acquired aplastic anemia is a clinical syndrome in which there is a deficiency of red cells, neutrophils, monocytes, and platelets in the blood, and fatty replacement of the marrow with a near absence of hematopoietic precursor cells. Reticulocytopenia is a constant feature. Neutropenia, monocytopenia, and thrombocytopenia, when severe, are life threatening because of the risk of infection and bleeding, complicated by severe anemia. Most cases occur without an evident precipitating cause and are the result of autoreactive cytotoxic T lymphocytes that suppress or destroy primitive CD34+ multipotential hematopoietic cells. The disorder also can occur after (1) prolonged high-dose exposure to certain toxic chemicals (eg, benzene); (2) after specific viral infections (eg, Epstein-Barr virus); (3) as an idiosyncratic response to certain pharmaceuticals (eg, ticlopidine, chloramphenicol); (4) as a feature of an autoimmune disorder (eg, lupus erythematosus); or, rarely, (5) in association with pregnancy. The final common pathway is through cytotoxic T-cell autoreactivity, whether idiopathic or associated with an inciting agent, because they all respond in a similar fashion to immunosuppressive therapy. The differential diagnosis of acquired aplastic anemia includes a hypoplastic marrow that can accompany paroxysmal nocturnal hemoglobinuria or hypoplastic oligoblastic (myelodysplastic syndrome) or polyblastic (acute) myelogenous leukemia. Allogeneic hematopoietic cell transplantation is curative in approximately 80% of younger patients with high-resolution human leukocyte antigen–matched sibling donors, although the posttransplant period may be complicated by severe graft-versus-host disease. The disease may be significantly ameliorated or sometimes cured by immunotherapy, especially a regimen coupling antithymocyte globulin with cyclosporine. However, after successful treatment with immunosuppressive agents, the disease may relapse or evolve into a clonal myeloid disorder, such as paroxysmal nocturnal hemoglobinuria, a clonal cytopenia, or oligoblastic or polyblastic myelogenous leukemia. The addition of eltrombopag to immunotherapy has increased the response rate and the quality of the response. Several uncommon inherited disorders, including Fanconi anemia (FA), Shwachman-Diamond syndrome, dyskeratosis congenita, and others have aplastic hematopoiesis as a primary manifestation.

ACQUIRED APLASTIC ANEMIA

DEFINITION AND HISTORY

Aplastic anemia is a clinical syndrome that results from a marked diminution of marrow blood cell production. The decrease in hematopoiesis results in reticulocytopenia, anemia, granulocytopenia, monocytopenia, and thrombocytopenia. The diagnosis usually requires the presence of pancytopenia with a neutrophil count fewer than 1.5 × 109/L, a platelet count fewer than 50 × 109/L, a hemoglobin concentration less than 100 g/L, and an absolute reticulocyte count fewer than 40 × 109/L, accompanied by a hypocellular marrow without abnormal or malignant cells or fibrosis.1 For the purpose of therapeutic decision making, comparative clinical trials, and international sharing of data, the disease has been stratified into moderately severe, severe, and very severe acquired aplastic anemia based on the blood counts (especially the neutrophil count) and the degree of marrow hypocellularity (Table 36–1). Most cases of aplastic anemia are acquired; many fewer cases are the result of an inherited disorder, such as ...

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