A normal pregnancy consumes 500-800 mg of iron from the mother. Premenopausal women have a high incidence of marginal iron stores or iron deficiency (ID), with or without anemia, particularly in the less developed world. Although pregnancy is associated with a "physiologic" anemia largely related to maternal volume expansion; it is paradoxically associated with an increase in erythrocyte production and erythrocyte mass/kg. ID is a limiting factor for this erythrocyte mass expansion and can contribute to adverse pregnancy outcomes. This review summarizes erythrocyte and iron balance observed in pregnancy; its implications and impact on mother and child; and provides an overview of approaches to the recognition of ID in pregnancy and its management, including clinically relevant questions for further investigation.

Pure red cell aplasia (PRCA) is a syndrome defined by a normocytic normochromic anemia with severe reticulocytopenia and marked reduction or absence of erythroid precursors from the bone marrow. Diamond-Blackfan anemia is a congenital form of PRCA. Acquired PRCA may be either a primary disorder or secondary to some other disorder or agent. Primary acquired PRCA is an autoimmune disorder that is frequently antibody-mediated. Myelodysplastic syndromes may also present with the morphologic appearance of PRCA. Secondary acquired PRCA may be associated with collagen vascular/autoimmune disorders such as systemic lupus erythematosus; lymphoproliferative disorders such as chronic lymphocytic leukemia or large granular lymphocyte leukemia; infections, particularly B19 parvovirus; thymoma and other solid tumors; or a variety of other disorders, drugs, or toxic agents. The therapeutic approach to PRCA typically involves immunosuppression, but specific pathogenic subtypes are associated with specific therapeutic approaches. Cyclosporine A, with or without concurrent corticosteroids, appears to be the single most effective immunosuppressive agent.

Improved understanding of the inflammatory response and the identification and characterization of the specific cytokines involved, as well as improved understanding of erythropoiesis, and the availability of recombinant human growth factors such as EPO, have greatly enhanced our appreciation of the pathogenesis of ACD by allowing development of a number of informative models for studying this syndrome. It appears that a variety of cytokines are involved in all aspects of the pathogenesis of ACD, from the inhibition of erythroid progenitors and EPO production to impairment of iron release. A schematic of the contributions of some of these cytokines to the development of ACD is shown in Fig 6. The exact biochemical mechanisms by which these effects occur is still to be determined. The progress outlined in this report has allowed us to develop a more precise understanding of the pathogenesis of this common and important clinical syndrome. In 1983, Hansen subtitled a review of ACD “A Bag of Unsolved Questions.” Although this description is still accurate, our understanding of ACD has now developed to the point where we can offer a more defined subtitle: “A Bag of Cytokines.”

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The anemia of chronic disease (ACD) results from 3 major processes: slightly shortened red cell survival, impaired reticuloendothelial system iron mobilization, and impaired erythropoiesis. Hepcidin is an acute-phase protein with specific iron regulatory properties, which, along with the anemia seen with increased hepcidin expression, have led many to consider it the major mediator of ACD. However, if hepcidin is the major factor responsible for ACD, then it should also contribute to the impaired erythropoiesis observed in this syndrome. Erythroid colony formation in vitro was inhibited by hepcidin at erythropoietin (Epo) concentrations less than or equal to 0.5 U/mL but not at Epo 1.0 U/mL. At Epo concentrations of 0.3 U/mL, HCD57 erythroleukemia cells exposed to hepcidin exhibit decreased expression of the antiapoptotic protein pBad compared with controls. These studies suggest that hepcidin may contribute to anemia in ACD not only through effects on iron metabolism, but also through inhibition of erythroid progenitor proliferation and survival.