Chapter 098. Iron Deficiency and Other Hypoproliferative Anemias (Part 4) Stages of Iron Deficiency Iron-deficiency anemia is the condition in which there is anemia and clear evidence of iron lack. The progression to iron deficiency can be divided into three stages (Fig. 98-2). The first stage is negative iron balance, in which the demands for (or losses of) iron exceed the body's ability to absorb iron from the diet. This stage results from a number of physiologic mechanisms, including blood loss, pregnancy (in which the demands for red cell production by the fetus outstrip the mother's ability to provide iron), rapid growth spurts in the adolescent, or inadequate dietary iron intake. Blood loss in excess of 10–20 mL of red cells per day is greater than the amount of iron that the gut can absorb from a normal diet. Under these circumstances the iron deficit must be made up by mobilization of iron from RE storage sites. During this period, iron stores—reflected by the serum ferritin level or the appearance of stainable iron on bone marrow aspirations— decrease. As long as iron stores are present and can be mobilized, the serum iron, total iron-binding capacity (TIBC), and red cell protoporphyrin levels remain within normal limits. At this stage, red cell morphology and indices are normal. Figure 98-2 Laboratory studies in the evolution of iron deficiency. 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. Patients with iron- deficiency anemia demonstrate all the same abnormalities plus hypochromic microcytic anemia. (From Hillman and Finch, with permission.) When iron stores become depleted, the serum iron begins to fall. Gradually, the TIBC increases, as do red cell protoporphyrin levels. By definition, marrow iron stores are absent when the serum ferritin level is <15 µg/L. As long as the serum iron remains within the normal range, hemoglobin synthesis is unaffected despite the dwindling iron stores. Once the transferrin saturation falls to 15–20%, hemoglobin synthesis becomes impaired. This is a period of iron-deficient erythropoiesis . Careful evaluation of the peripheral blood smear reveals the first appearance of microcytic cells, and if the laboratory technology is available, one finds hypochromic reticulocytes in circulation. Gradually, the hemoglobin and hematocrit begin to fall, reflecting iron-deficiency anemia. The transferrin saturation at this point is 10–15%. When moderate anemia is present (hemoglobin 10–13 g/dL), the bone marrow remains hypoproliferative. With more severe anemia (hemoglobin 7–8 g/dL), hypochromia and microcytosis become more prominent, target cells and misshapen red cells (poikilocytes) appear on the blood smear as cigar- or pencil- shaped forms, and the erythroid marrow becomes increasingly ineffective. Consequently, with severe prolonged iron-deficiency anemia, erythroid hyperplasia of the marrow develops, rather than hypoproliferation. Causes of Iron Deficiency Conditions that increase demand for iron, increase iron loss, or decrease iron intake or absorption can produce iron deficiency (Table 98-2). Table 98-2 Causes of Iron Deficiency Increased demand for iron and/or hematopoiesis rapid growth in infancy or adolescence pregnancy erythropoietin therapy Increased iron loss chronic blood loss menses acute blood loss blood donation phlebotomy as treatment for polycythemia vera Decreased iron intake or absorption inadequate diet malabsorption from disease (sprue, Crohn's disease) malabsorption from surgery (post-gastrectomy) acute or chronic inflammation . Chapter 098. Iron Deficiency and Other Hypoproliferative Anemias (Part 4) Stages of Iron Deficiency Iron- deficiency anemia is the condition in which there is anemia and clear. of Iron Deficiency Conditions that increase demand for iron, increase iron loss, or decrease iron intake or absorption can produce iron deficiency (Table 98-2). Table 98-2 Causes of Iron Deficiency. cell morphology and indices are normal. Figure 98-2 Laboratory studies in the evolution of iron deficiency. Measurements of marrow iron stores, serum ferritin, and total iron- binding capacity