HYPOPROLIFERATIVE ANEMIAS

HYPOPROLIFERATIVE ANEMIAS is a topic covered in the Harrison's Manual of Medicine.

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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. 62-1). RBC morphology is generally normal until iron deficiency is severe (see below).

FIGURE 62-1

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. In older people, erythropoietin levels normally increase to maintain normal hemoglobin levels. If this increase does not happen, anemia may develop. About 11% of community-dwelling adults over age 65 and up to 45% of nursing home residents have this aging-related anemia. It is a relative erythropoietin deficiency without renal disease. 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 62-1 may assist in the differential diagnosis of hypoproliferative anemias. Measurement of hepcidin in the urine is not yet practical or widely available.

TABLE 62-1: DIAGNOSIS OF HYPOPROLIFERATIVE ANEMIAS
TestsIron DeficiencyInflammationRenal DiseaseHypometabolic StatesAnemia of Aging
AnemiaMild to severeMildMild to severeMildMild
MCV (fL)60–9080–90909080–90
MorphologyNormomicrocyticNormocyticNormocyticNormocyticNormocytic
SI<30<50NormalNormalNormal
TIBC>360<300NormalNormalNormal
Saturation (%)<1010–20NormalNormalNormal
Serum ferritin (μg/L)<1530–200115–150NormalNormal
Iron stores02–4+1–4+NormalNormal
Erythropoietin levelsHighNormal or HighLowNormal or LowNormal
Abbreviations: MCV, mean corpuscular volume; SI, serum iron; TIBC, total iron-binding capacity.

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TY - ELEC T1 - HYPOPROLIFERATIVE ANEMIAS ID - 623585 Y1 - 2017 PB - Harrison's Manual of Medicine UR - https://harrisons.unboundmedicine.com/harrisons/view/Harrisons-Manual-of-Medicine/623585/all/HYPOPROLIFERATIVE_ANEMIAS ER -