Anemia - Iron-Deficiency Diagnostics

Laboratory Tests and Ancillaries

Lab Exam  

CBC is done to determine the mean corpuscular volume (MCV) or RBC size. Iron-deficiency anemia has decreased MCV, and reticulocyte count with increased red cell distribution width (RDW). A normal MCV in patients with iron-deficiency anemia will require further testing with serum ferritin. The serum markers of iron deficiency include low ferritin, low transferrin saturation (TS), low serum iron, increased TIBC, increased erythrocyte protoporphyrin (FEP), and increased sTfR.   Serum ferritin level measurement is the most common, sensitive and specific, and easily available test to confirm iron-deficiency anemia. Ferritin is an acute phase reactant and reflects iron stores in otherwise healthy adults. It can be elevated in patients with chronic inflammation or infection; thus, this test should be done in the absence of inflammation. Serum ferritin levels of <70 ng/mL in adults may be used to diagnose iron deficiency in patients with inflammation or infection. Other lab tests (eg C-reactive protein, serum iron, soluble transferrin receptor or transferrin saturation) may be needed along with ferritin to diagnose iron-deficiency anemia in patients with inflammatory conditions. It is useful in pregnant women who often have an elevated serum transferrin in the absence of iron deficiency. In an anemic adult, a ferritin level of <15 ng/mL is diagnostic of iron deficiency, and levels between 15 and 30 ng/mL are highly suggestive. For pregnant women, the most commonly used thresholds of serum ferritin are <12 ng/mL and <15 ng/mL for the diagnosis of iron deficiency. In the GI evaluation of iron-deficiency anemia, the American Gastroenterological Association in 2020 recommends a cutoff ferritin level of <45 ng/mL as diagnostic of iron deficiency. Lower thresholds from 10 to 12 ng/mL have been used in children. This test replaced bone marrow assessment of iron stores which was the gold standard for the diagnosis of iron-deficiency anemia.

Soluble transferrin receptor level is elevated in patients with iron-deficiency anemia. This test can be done if the diagnosis remains unclear. It is an indirect measure of erythropoiesis. It is unaffected by inflammatory states. It must be noted that in pregnant women and those taking contraceptives, transferrin is elevated in the absence of iron deficiency.  

Transferrin saturation is a complementary test to diagnose iron-deficiency anemia. It reflects the amount of iron available for erythropoiesis. One of the earliest biomarkers of iron deficiency is a decrease in the transferrin saturation.  

Erythrocyte protoporphyrin is a heme precursor and accumulates in the absence of adequate iron stores. Zinc protoporphyrin reflects the insufficiency if iron supply in the last stages of hemoglobin synthesis. If the other tests are indeterminate and suspicion for iron-deficiency anemia remains, the absence of stable iron stores in a bone marrow biopsy is considered the diagnostic standard. 

Anemia - Iron-Deficiency_Diagnostics

Imaging

Endoscopy  

Endoscopy helps identify GI tract lesions which cause iron-deficiency anemia from occult bleeding. Evaluation should be site-directed in patients with GI symptoms. If gynecological workup in premenopausal women is negative and the patient does not respond to iron therapy, endoscopy should be performed to exclude an occult GI source. A bidirectional endoscopy, including esophagogastroduodenoscopy and colonoscopy, is recommended over no endoscopy in asymptomatic men and pre- and postmenopausal women with iron-deficiency anemia. The benefits of identifying GI disorders and malignancy in these individuals outweigh the risks of the procedure. If the initial bidirectional endoscopy in asymptomatic patient does not identify a lesion, a trial of iron therapy may be started. Consider further evaluation (eg non-invasive testing H pylori, capsule endoscopy) if the trial of iron therapy did not correct iron-deficiency anemia.