Anemia is a common clinical problem in medicine. A physiologic approach (outlined in Chap. 51) provides the most efficient path to diagnosis and management. Anemias arise either because red blood cell (RBC) production is inadequate or because RBC lifespan (normally 120 days) is shortened through loss from the circulation or destruction.
These are the most common anemias. Usually the RBC morphology is normal and the reticulocyte index (RI) is low. Marrow damage, early iron deficiency, and decreased erythropoietin production or action may produce anemia of this type.
Marrow damage may be caused by infiltration of the marrow with tumor or fibrosis that crowds out normal erythroid precursors or by the absence of erythroid precursors (aplastic anemia) as a consequence of exposure to drugs, radiation, chemicals, viruses (e.g., hepatitis), autoimmune mechanisms, or genetic factors, either hereditary (e.g., Fanconi's anemia) or acquired (e.g., paroxysmal nocturnal hemoglobinuria). Most cases of aplasia are idiopathic. The tumor or fibrosis that infiltrates the marrow may originate in the marrow (as in leukemia or myelofibrosis) or be secondary to processes originating outside the marrow (as in metastatic cancer or myelophthisis).
Early iron-deficiency anemia (or iron-deficient erythropoiesis) is associated with a decrease in serum ferritin levels (<15 μg/L), moderately elevated total iron-binding capacity (TIBC) (>380 μg/dL), serum iron (SI) level <50 μg/dL, and an iron saturation of <30% but >10% (Fig. 68-1). RBC morphology is generally normal until iron deficiency is severe (see below).
Measurements of marrow iron stores, serum ferritin, and total iron-binding capacity (TIBC) are sensitive to early iron-store depletion. Iron-deficient erythropoiesis is recognized from additional abnormalities in the serum iron (SI), percent transferrin saturation, the pattern of marrow sideroblasts, and the red cell protoporphyrin level. Pts with iron-deficiency anemia demonstrate all the same abnormalities plus hypochromic microcytic anemia. (From RS Hillman, CA Finch: Red Cell Manual, 7th. ed, Philadelphia, Davis, 1996, with permission.)
Decreased stimulation of erythropoiesis can be a consequence of inadequate erythropoietin production [e.g., renal disease destroying the renal tubular cells that produce it or hypometabolic states (endocrine deficiency or protein starvation) in which insufficient erythropoietin is produced] or of inadequate erythropoietin action. The anemia of chronic disease is a common entity. It is multifactorial in pathogenesis: inhibition of erythropoietin production, inhibition of iron reutilization (which blocks the response to erythropoietin), and inhibition of erythroid colony proliferation by inflammatory cytokines (e.g., tumor necrosis factor, interferon γ). Hepcidin, a small iron-binding molecule produced by the liver during an acute-phase inflammatory response, may bind iron and prevent its reutilization in hemoglobin synthesis. The laboratory tests shown in Table 68-1 may assist in the differential diagnosis of hypoproliferative anemias. Measurement of hepcidin in the urine is not yet practical or widely available.
TABLE 68-1DIAGNOSIS OF HYPOPROLIFERATIVE ANEMIAS