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Arch Hellen Med, 17(3), May-June 2000, 256-272


Acquired and inherited aplastic anemia in childhood.
Progress in diagnosis and understanding
of the pathogenetic mechanisms

Department of Pediatric Hematology-Oncology, “Aghia Sophia” Children’s Hospital, Athens, Greece

Aplastic anemia (AA) of childhood represents a rare nosologic entity which belongs to the bone marrow failure syndromes and is classified as acquired and inherited, either congenital or not. The bulk of evidence regarding the pathogenesis of AA indicates a severe defect of the stem cell (SC) compartment resulting in a disturbance of the SC populating capacity, proliferation, division and differentiation rate and in a substantial reduction of SC numbers. Two pathways of bone marrow damage are hypothesized: Type I involves DNA impairment of the most primitive hematopoietic SC at the top of hierarchy of hematopoiesis, by irradiation, radiomimetic agents such as busulphan and other drugs, while Fanconi's anemia is an inherited example of type I damage with inability to repair DNA defects. Type II is due to damage at the level of the more mature hematopoietic cell, involving the cell membrane or metabolism, by a variety of drugs, viruses and immune mechanisms. For most cases of acquired AA an underlying mechanism of immune destruction of hematopoietic progenitors is prevalent (loss of immune tolerance leading to an abnormal reaction and immune mediated SC catastrophe). The participation of alterations of stromal factors, such as defect of stromal cells or inadequate local action of hematopoietic growth factors, in the pathophysiologic process, seems to be of minor importance. Theoretically, overt clinical manifestation of the acquired disease is preceded by a toxic effect on bone marrow stem cells exerted by a specific factor. In the majority of cases however, no etiologic factor is isolated, and most of the cases of acquired AA are categorized as idiopathic. In the inherited form of the disease, the clinical manifestations of bone marrow aplasia of one or more cell lines may develop at any age. Moreover, there is diversity regarding the SC defect and the underlying pathogenetic mechanisms. Fanconi's anemia and dyskeratosis congenita represent the most common types of inherited AA. The onset of the disease can be insidious or acute, and patients may have an acute, transient or chronic course. The clinical features and laboratory findings are in most cases common to both types of AA, acquired or inherited, depending on whether the defect involves one or all cell lines. The severity of the disease, its symptoms and signs depend on the degree of anemia, the neutropenia, and thrombocytopenia. In inherited AA (e.g. Fanconi's anemia), physical examination often, but not always, reveals characteristic findings related to the underlying nosologic entity (malformations of the skeleton and urinary tract, growth retardation etc.). In this review current data on the classification, etiology, pathogenetic mechanisms, and association of acquired AA with other clonal diseases (e.g. myelodysplastic syndromes or leukemia) are discussed. Brief reference is made to the most frequent types of inherited AA diagnosed during childhood and recent research development concerning their pathogenesis.

Key words: Aplastic anemia, Bone marrow failure syndromes, Childhood, Etiology, Pathogenetic mechanisms.

© 2000, Archives of Hellenic Medicine