Anemia in chronic disease: causes, symptoms, diagnosis, treatment

Anemia of chronic disease (anemia of impaired iron reutilization) is multifactorial and often associated with iron deficiency. Diagnosis usually requires the presence of chronic infection, inflammation, cancer, microcytic or borderline normocytic anemia, and serum transferrin and ferritin levels between those typical of iron deficiency anemia and sideroblastic anemia. Therapy is directed at the underlying disease and, if irreversible, erythropoietin.

Worldwide, anemia of chronic disease is the second most common. In the early stages, red blood cells are normochromic, but over time they become microcytic. The main problem is the failure of the erythroid series of the bone marrow to proliferate in response to anemia.

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Causes anemia in chronic disease

This type of anemia should be suspected in the presence of a chronic disease, most often an infectious, inflammatory process (especially rheumatoid arthritis) or a malignant neoplasm, but a similar process occurs with any infection or inflammation.

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Pathogenesis

Three pathophysiological mechanisms are distinguished:

• moderate shortening of red blood cell survival time for reasons that are still unclear in patients with cancer or chronic granulomatous infections;
• disruption of erythropoiesis due to a decrease in EPO production and the bone marrow's response to it;
• violation of intracellular iron metabolism.

Reticular cells retain iron derived from old red blood cells, making it unavailable for hemoglobin synthesis; thus, compensation of anemia by increasing red blood cell production is impossible. Macrophage cytokines (e.g., IL-1, tumor necrosis factor-a, interferon) in patients with infection, inflammation, and cancer cause or contribute to a decrease in EPO production and impair iron metabolism.

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Symptoms anemia in chronic disease

Clinical manifestations are usually those that define the underlying disease (infection, inflammation or malignancy).

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Diagnostics anemia in chronic disease

Anemia of chronic disease is suspected in patients with microcytic or borderline normocytic anemia with chronic infection, inflammation, or cancer. If chronic anemia is suspected, serum iron, transferrin, transferrin receptor, and serum ferritin should be measured. The hemoglobin level usually exceeds 80 g/L unless additional processes cause the anemia to progress. If there is an iron deficiency state in addition to the chronic disease, the serum ferritin level is usually less than 100 ng/mL, and if the ferritin level is slightly less than 100 ng/mL in the presence of infection, inflammation, or malignancy, iron deficiency is assumed to coexist with the anemia of chronic disease. However, given the possibility of a false increase in serum ferritin levels as an acute phase marker, in cases of high serum ferritin levels (> 100 ng/ml), determination of the serum transferrin receptor helps in the differential diagnosis of iron deficiency and anemia in the setting of chronic disease.

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Treatment anemia in chronic disease

The most important thing is to treat the underlying disease. Since the anemia is usually mild, transfusions are usually not required and recombinant EPO is sufficient. Taking into account both the decreased production of erythropoietin and the presence of bone marrow resistance to it, the dose of the latter can be increased from 150 to 300 U/kg subcutaneously 3 times a week. A good response is likely if after 2 weeks of therapy the hemoglobin level increases by more than 0.5 g/dL and the serum ferritin is less than 400 ng/mL. Iron supplementation is necessary to obtain an adequate response to EPO.