ANEMIA OF CHRONIC DISEASE

Many chronic systemic diseases are associated with mild or moderate anemia. Common causes include chronic infection or inflammation, cancer, and liver disease. The anemia of chronic renal failure is somewhat different in pathophysiology, involving reduced production of erythropoietin, and is usually more severe. Hepcidin has been identified as an important mediator of sequestration of iron within macrophages, and upregulation of hepcidin in response to mediators of inflammation, such as IL-6, is an important cause of anemia of chronic disease.
Clinical Findings
SYMPTOMS AND SIGNS
The clinical features are those of the causative condition. The diagnosis should be suspected in patients with known chronic diseases; it is confirmed by the findings of low serum iron, low TIBC, and normal or increased serum ferritin (or normal or increased bone marrow iron stores). In cases of significant anemia, coexistent iron deficiency or folic acid deficiency should be suspected. Decreased dietary intake of folate or iron is common in these ill patients, and many will also have ongoing gastrointestinal blood losses. Patients undergoing hemodialysis regularly lose both iron and folate during dialysis.
LABORATORY FINDINGS
The hematocrit rarely falls below 60% of baseline (except in renal failure). The MCV is usually normal or slightly reduced. Red blood cell morphology is nondiagnostic, and the reticulocyte count is neither strikingly reduced nor increased. Serum iron values may be unmeasurable, and transferrin saturation may be extremely low, leading to an erroneous diagnosis of iron deficiency. In contrast to iron deficiency, serum ferritin values should be normal or increased. A serum ferritin value of less than 30 mcg/L should suggest coexistent iron deficiency.
Treatment
In most cases no treatment is necessary. Purified recombinant erythropoietin (epoetin alfa) is effective for treatment of the anemia of renal failure and other secondary anemias such as anemia related to cancer or inflammatory disorders (eg, rheumatoid arthritis). In renal failure, optimal response to epoetin alfa requires adequate intensity of dialysis. Epoetin alfa must be injected subcutaneously and is very expensive. One effective schedule is 30,000 units once weekly. This agent is used only when the patient is transfusion dependent or when the quality of life is clearly improved by the hematologic response.

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