To address these concerns, researchers developed a ferritin index, a calculated ratio of sTfR:log ferritin, to provide a more accurate indicator of true iron deficiency in patients with anemia of inflammation. A low ratio indicates anemia of inflammation, while a higher index reveals true iron-deficiency anemia in association with anemia of inflammation. Unfortunately at this time, the cutoff value is largely dependent on the specific diagnostic test used, and some clinicians may find interpretation difficult.8 However, some evidence suggests that when used correctly the test can help improve the clinical diagnosis of iron-deficiency anemia, especially in the presence of inflammatory disease.9
Another potentially helpful test is reticulocyte hemoglobin content (CHr), which predicts iron availability for erythropoiesis. It tends to be reduced in anemia of inflammation present along with iron-deficiency anemia compared to anemia of inflammation alone. However, the test shows some overlap between anemia of inflammation alone and anemia of inflammation present with iron deficiency, and the determination may be limited based on the specific technical equipment. The percentage of hypochromic cells can also provide an indicator of iron availability (showing a higher percentage in true iron deficiency), but determination is dependent on the specific equipment.1,8
However, simple indices, such as mean corpuscular hemoglobin and mean cellular volume, can also be helpful, although their diagnostic sensitivity and specificity for iron-deficiency anemia are lower than for a ferritin index.1,8
Mark Koury, MD, is a practicing hematologist and an emeritus professor of medicine at Vanderbilt University School of Medicine in Nashville. In his own approach to diagnosis, Dr. Koury tends to first look at whether or not microcytosis is present. “I would say that most people who have chronic conditions seen by rheumatologists probably have normocytic anemia, not microcytic. When microcytic anemia occurs, I am always concerned about iron deficiency. And of course that occurs in rheumatology patients for a number of reasons. They’ve been bleeding in most cases; they’ve been taking NSAIDs or steroids that results in occult bleeding. They may have had a large number of lab tests, and blood taken for diagnostic testing can actually contribute to iron deficiency.”
Dr. Koury explains that in anemia of inflammation, high hepcidin keeps iron in the red cell precursors for a longer period of time than in simple iron deficiency, so microcytosis doesn’t occur as rapidly. “I use MCV; some people might use MCH, but basically these RBC indices give you a good hint to whether or not a patient has iron deficiency overlapping with anemia of chronic disease. If you see a declining MCV over a period of months, I would be concerned, especially when you dip down to 80 femtoliters or so. That’s a sign that the patient is getting iron deficient.”