title: Pathophysiology of aplastic anaemia.
abstract: No single pathophysiological phenomenon--neither the intrinsic defect of haemopoiesis nor any of the described immune effects--explains aplastic anaemia. Since the intrinsic defect is compatible with near normal haemopoietic function, as seen in autologous bone marrow reconstitution, it cannot be the cause of severe pancytopenia. On the other hand, immune mechanisms cannot be the primary cause of the disease, otherwise haemopoietic function would recover to complete normality after immunosuppressive therapy. From these observations we deduce that the intrinsic defect, a premalignant haemopoietic disorder, can either be clinically quiescent by virtue of repair mechanisms, or induce auto-reactivity of the immune system against the abnormal haemopoietic tissue, drugs, chemicals and viruses acting as non-specific triggers or amplifiers. In this sense, aplastic anaemia could be interpreted as an attempt to 'self-cure' from a variant type of preleukaemia. This means that the original concept of aplastic anaemia being a hypoplastic variant of leukaemia may be true. The fact that aplastic anaemia can present either as acute severe bone marrow failure, as chronic mild pancytopenia or as a myelodysplasia-like syndrome does not imply that the underlying pathophysiological mechanisms are basically different. Variations of the clinical course and the response to immunosuppressive treatment could be explained by variations in the balance between the primary defect and the secondary immune reaction; the co-involvement of accessory cells in the primary disease; the relative time course of the two components and the efficiency of repair mechanisms. From repeated in vitro studies in a large group of aplastic anaemia patients at various stages of disease this concept can be applied to the majority of cases, including chloramphenicol- and virus-induced aplastic anaemia. In a small proportion of patients with pancytopenia occurring after exposure to certain drugs other than chloramphenicol, aplastic anaemia is rapidly and completely reversible after withdrawal of the drug. These patients probably have truly benign aplastic anaemia and thus differ from the majority of patients who are left with a permanently fragile bone marrow once they have acquired aplastic anaemia.
authors.forename: C
authors.initials: C
authors.lastname: Nissen-Druey
mesh_terms: D000741:Anemia, Aplastic / Q000209:etiology / Q000503:physiopathology*; D000906:Antibodies / Q000276:immunology; D006410:Hematopoiesis; D006412:Hematopoietic Stem Cells; D006801:Humans; D008222:Lymphokines / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology
chemical_list: D000906:Antibodies; D008222:Lymphokines