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ESSENTIALS OF DIAGNOSIS

ESSENTIALS OF DIAGNOSIS

  • Mild or moderate normocytic or microcytic anemia.

  • Normal or increased ferritin and normal or reduced transferrin.

  • Underlying chronic disease.

GENERAL CONSIDERATIONS

Many chronic systemic diseases are associated with mild or moderate anemia. The anemias of chronic disease are characterized according to etiology and pathophysiology. First, the anemia of inflammation is associated with chronic inflammatory states (such as IBD, rheumatologic disorders, chronic infections, and malignancy) and is mediated through hepcidin (a negative regulator of ferroportin) primarily via elevated IL-6, resulting in reduced iron uptake in the gut and reduced iron transfer from macrophages to erythroid progenitor cells in the bone marrow. This is referred to as iron-restricted erythropoiesis since the patient is iron replete. There is also reduced responsiveness to erythropoietin, the elaboration of hemolysins that shorten RBC survival, and the production of other inflammatory cytokines that dampen RBC production. The serum iron and iron saturation are low in the anemia of inflammation. Second, the anemia of organ failure can occur with kidney disease, liver failure, and endocrine gland failure. Erythropoietin production is reduced and the RBC mass decreases in response to the diminished signal for RBC production; the serum iron is normal (except in CKD where it is low due to the reduced hepcidin clearance and subsequent enhanced degradation of ferroportin). Third, the anemia of older adults is present in up to 20% of individuals over age 85 years in whom a thorough evaluation for an explanation of anemia is negative. The anemia is a consequence of (1) a relative resistance to RBC production in response to erythropoietin, (2) a decrease in erythropoietin production relative to the nephron mass, (3) a dampening of erythropoiesis due to high levels of chronic inflammatory cytokines in older adults, and/or (4) the presence of various somatic pathogenic variants in myeloid genes typically associated with myeloid neoplasms. The latter condition is now referred to as clonal cytopenias of undetermined significance, which has a 15–20% per year rate of transformation to a myeloid neoplasm, such as a myelodysplastic syndrome (MDS). The serum iron is normal.

CLINICAL FINDINGS

A. Symptoms and Signs

The clinical features are those of the causative condition and anemia. The diagnosis should be suspected in patients with known chronic diseases. In cases of significant anemia, coexistent iron deficiency, folic acid deficiency, or vitamin B12 deficiency should be suspected. Decreased dietary intake of iron or folic acid is common in chronically ill patients, many of whom will also have ongoing GI blood losses. Patients undergoing hemodialysis regularly lose both iron and folic acid during dialysis.

B. Laboratory Findings

The hematocrit rarely falls below 60% of baseline (except in kidney failure). The MCV is usually normal or slightly reduced. RBC morphology is usually normal, and the reticulocyte count is mildly ...

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