Plasma Ferritin Concentrations

Plasma ferritin concentrations are helpful in the detection of both iron deficiency and iron overload.¹ Plasma ferritin concentrations decline with storage iron depletion; a plasma ferritin concentration less than 12 mg/L is virtually diagnostic of absence of iron stores. The only known conditions that may lower the plasma ferritin concentration independently of a decrease in iron stores are hypothyroidism and ascorbate deficiency, but these conditions only rarely cause problems in clinical interpretation. Increased plasma ferritin concentrations may indicate increased storage iron, but a number of disorders may increase the plasma ferritin level independently of the body iron store. Plasma ferritin is an acute-phase reactant with increased ferritin synthesis, a nonspecific response that is part of the general pattern of the systemic effects of inflammation.^1,2 Thus, fever, acute infections, rheumatoid arthritis, and other chronic inflammatory disorders elevate the plasma ferritin concentration. Both acute and chronic damage to the liver, as well as to other ferritin-rich tissues, may increase plasma ferritin concentration through an inflammatory process or by releasing tissue ferritins from damaged parenchymal cells.¹

Table 8-1 Causes of Iron Deficiency

Iron Deficiency and Coexisting Disorders

Detection of iron deficiency in the presence of chronic infectious, inflammatory, or malignant disorders that increase plasma hepcidin is more problematic than in the absence of such disorders.² Even if iron lack contributes to the anemia of chronic disorders, the increase in plasma hepcidin will lead to a fall in the transferrin concentration (or total iron-binding capacity) and an increase in the plasma ferritin concentration.^2,3 Because the serum transferrin receptor concentration is less affected by inflammation, its measurement usually can determine whether iron stores are absent.⁴ If uncertainty remains, BM examination is definitive. If iron deficiency is present, iron stores are absent; if the anemia of chronic disorders alone is responsible, iron stores are present and typically increased.

Therapeutic Trial of Iron

The diagnosis of iron deficiency often is confirmed by the outcome of a therapeutic trial of iron. A specific orderly response to, and only to, treatment with iron constitutes the final definitive proof that a lack of iron is the cause of anemia. The unequivocal diagnostic response consists of (1) a reticulocytosis, which begins approximately 3 to 5 days after adequate iron therapy is instituted, reaches a maximum on days 8 to 10, and then declines; and (2) a significant increase in hemoglobin concentration, which should begin shortly after the reticulocyte peak, is invariably present by 3 weeks after iron therapy is begun, and persists until the hemoglobin concentration is restored to normal. The result of a therapeutic trial of iron must be evaluated for possible confounding factors, such as poor compliance with iron therapy; malabsorption of therapeutic iron; continuing blood loss; and the effects of coexisting conditions, especially infectious, inflammatory, or malignant disorders. The therapeutic trial merely aids in establishing the presence of iron deficiency. The search for underlying causes of iron deficiency must continue despite a positive response to iron therapy.

Figure 8-1 IRON-DEFICIENCY ANEMIA.

Peripheral blood smear (A and B), bone marrow (BM) aspirate (C), and Prussian blue stain of BM aspirate (D) with control from a 16-year-old girl with hemoglobin 6.7 g/dL, hematocrit 22.6%, and mean corpuscular volume 59.2 fL. Peripheral smear shows hypochromic microcytic red blood cells (A), with widening of the central pallor and “pencil” cells (B). Polychromatophilic erythroid precursors in the aspirated specimen have scanty cytoplasm that is irregular and vacuolated (C). The Prussian blue–stained aspirate shows no iron stores in multiple spicules (D). Care must be taken not to overinterpret positive staining debris on top of cells (center)

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