Bone marrow failure can be inherited or acquired. It can involve just 1 cell line or all 3 cell lines. The pathophysiology of these defects includes the following mechanisms of action: (1) a decrease in or damage to the hematopoietic stem cells and their microenvironment, resulting in hypoplastic or aplastic bone marrow; (2) maturation defects, such as vitamin B-12 or folate deficiency; and (3) differentiation defects, such as myelodysplasia.
Generally, hematopoietic stem cells are damaged by a congenital defect or exposure to a noxious substance or factor. Pathophysiologic mechanisms are (1) an acquired stem cell injury from viruses, toxins, or chemicals that leads to a quantitative or qualitative abnormality; (2) abnormal humoral or cellular control of hematopoiesis; (3) an abnormal or hostile marrow microenvironment; (4) immunologic suppression of hematopoiesis (ie, mediated by antibodies, T cells [or cellularly], or lymphokines); and (5) mutations in genes, causing inherited bone marrow failure syndromes. Identification of these relevant mutations has led to progress in defining the precise functions of the corresponding proteins in normal cells.