Diagnostic Approach to Anemia of Chronic Disease

Initial Evaluation

The American Journal of Kidney Diseases recommends beginning the diagnostic work-up with a complete blood count (CBC) with red cell indices, reticulocyte count, iron studies, and inflammatory markers to differentiate anemia of chronic disease from other causes and identify coexisting iron deficiency 1, 2
A CBC with differential and red cell indices is essential to characterize the anemia morphologically, with anemia of chronic disease typically being normocytic and normochromic 3
The reticulocyte count, corrected for the degree of anemia, assesses bone marrow response, with a low or inappropriately normal reticulocyte count indicating impaired erythropoiesis characteristic of anemia of chronic disease 1, 3

A complete iron panel, including serum iron, TIBC, ferritin, and transferrin saturation, helps distinguish anemia of chronic disease from iron deficiency, with anemia of chronic disease typically having low serum iron, low-normal TIBC, and normal-to-elevated ferritin 3, 4
Inflammatory markers, such as CRP or ESR, confirm the presence of chronic inflammation and aid in interpreting ferritin levels, as ferritin is an acute phase reactant that can be falsely elevated by inflammation 2, 4

The National Kidney Foundation suggests that pure anemia of chronic disease is characterized by low serum iron, low-normal TIBC, normal-to-elevated ferritin, and elevated inflammatory markers, while coexisting iron deficiency is indicated by low ferritin, low transferrin saturation, and elevated TIBC 3, 4
Functional iron deficiency, common in chronic disease, is suggested by ferritin >100 μg/L but transferrin saturation <20% 3, 4

The American Journal of Kidney Diseases recommends screening for other reversible causes, including vitamin B12 and folate levels if macrocytosis is present, thyroid function tests, and renal function tests 3, 5, 6
A stool guaiac test is recommended if there is any suggestion of gastrointestinal bleeding 3, 6

The American College of Physicians advises against assuming normal ferritin excludes iron deficiency in inflammatory states and delaying iron studies to check other tests first 4
Empiric iron supplementation should not be started without confirming the diagnosis, and combined deficiencies should not be overlooked 1, 2, 5