Anemia of chronic disease (ACD) can be difficult to diagnose, and is largely a diagnosis of exclusion. It may occur mixed with other anemias.


Features of anemia of chronic disease:

(1) exclusion of other types of anemia, or a level of anemia not totally explained by a condition associated with anemia

(2) no hematologic response to iron therapy, with adequate absorption

(3) presence of systemic disorder, usually chronic but occasionally acute

(4) anemia

(5) abnormalities of iron stores

(6) increased serum levels of cytokines (IL-1, TNF, etc.), possibly causing decreased red blood cell survival, abnormal iron metabolism and/or reduced hematopoiesis


The first step is to exclude other conditions:

(1) iron deficiency

(2) thalassemia

(3) hypothyroidism

(4) infiltration of the bone marrow (fibrosis, tumor, granulomatous inflammation)

(5) lead poisoning


Identification of a systemic disorder:

(1) ACD is usually associated with acute or chronic infection, an inflammatory disease, renal insufficiency, or a malignancy. However, anemic patients with these conditions may not have ACD.

(2) ACD may occur in other systemic conditions.


Features of the anemia:

(1) hematocrit < 40% for males, < 37% for females; usually mild but may be < 25% (Cash and Sears)

(2) usually normocytic but may be mildly microcytic; not macrocytic

(3) low reticulocyte index (decreased red blood cell production)

(4) increased RBC production with administration of exogenous erythropoietin, even if serum levels normal prior to the administration. This suggests a relative deficiency of erythropoietin.


Abnormalities of iron stores:

(1) serum iron reduced (probably can include patients at the low end of the normal reference range). The lower the serum iron level, the more iron deficiency should be considered.

(2) increased serum ferritin: Cash and Sears use a serum ferritin > 50 ng/mL to define ACD, but others argue that a higher value should be used since ferritin is an acute phase reactant. A serum ferritin < 10 ng/mL indicates iron deficiency.

(3) normal or increased iron in bone marrow stores

(4) The serum transferrin level and percent saturation of iron binding capacity may be decreased, but these are not useful in differentiating iron deficiency from ACD.



(1) Iron staining of the bone marrow needs to be done and interpreted carefully. Smears may be more reliable than sections of core biopsies.

(2) Distinction of early iron deficiency from ACD can be difficult.


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