ANEMIA OF CHRONIC DISEASE

     The anemia of chronic disease is associated with an inadequate marrow response as manifests by an inappropriately low reticulocyte response.  This type of anemia is generally normochromic and normocytic, but may become mildly hypochromic and microcytic and therefore is difficult to distinguish from iron deficiency anemia.  Acute illnesses may also be associated with this type of anemia especially bacterial infections and collagen vascular disorders, but the anemia resolves with treatment of the underlying disorder.

     Associated laboratory abnormalities include the above mentioned normochromic, normocytic anemia (although severe cases may be associated with a mild hypochromic, microcytic anemia) with an inappropriately low reticulocyte response.  The serum ferritin, iron and TIBC are helpful in establishing the diagnosis.  As opposed to iron deficiency anemia in which case the serum ferritin and iron are depressed with an associated elevation of the TIBC, the characteristic pattern of iron studies in anemia of chronic disease includes a low serum iron and TIBC with a normal to elevated serum ferritin.  Bone marrow aspirates stained with Prussian blue are only required when the diagnosis is in doubt.  In iron deficient states, there will be no stainable iron appreciated; however, in anemia of chronic disease, there will be normal or increased amounts of marrow iron appreciated with the Prussian blue stain.  However, bone marrow studies are invasive, so in cases where the diagnosis is in doubt, the erythrocyte sedimentation rate (ESR) may prove helpful.  When it is suspected that the serum ferritin is spuriously elevated with underlying iron deficiency anemia the ESR may be used to correct for the degree of inflammation.  When the serum ferritin is in excess of 80 ng/mL, iron deficiency anemia may be excluded with relative confidence.  However, if the serum ferritin is between 12 to 80 ng/mL with underlying inflammation and microcytic anemia, the accepted lower limit of normal for the serum ferritin value may be corrected for via the following equation:

                             ESR/2 + 5 = corrected lower limit of normal for serum ferritin

If the actual serum ferritin is greater than the calculated lower limit, iron deficiency is unlikely and the anemia is most likely secondary to chronic disease or an acute illness.  However, if the serum ferritin is less than the calculated lower limit for the degree of inflammation, iron deficiency is still likely. Other helpful tests which may obviate the need for bone marrow examination, include the serum transferrin receptor assay and the red blood cell protoporphyrin. If either is elevated, then iron deficiency is the diagnosis.

     Therapy is generally aimed at correcting the underlying disease state, or administering blood transfusions when dictated by symptoms.  When there is anemia of chronic disease secondary to underlying AIDS infection, patients with a serum erythropoietin level less than 500 IU/liter may respond to recombinant erythropoietin.  Patients who do respond to this form of therapy should be given concomitant oral iron supplementation during therapy.