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 TS, low serum iron, increased TIBC, increased free 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 reflects total body iron stores in otherwise healthy adults. In children ≥5 years old and adults, 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 ferritin cutoff level of <45 ng/mL as diagnostic of iron deficiency. In children <5 years old, lower thresholds of <12 ng/mL have been used.  

It is also important to note that ferritin is an acute phase reactant and can be elevated in patients with chronic inflammation or infection, potentially masking iron deficiency; thus, this test should be done in the absence of inflammation. Serum ferritin levels of <70-100 ng/mL may be used to diagnose iron deficiency in older children and adult patients with systemic inflammation or infection. In children <5 years old, lower thresholds of <30 ng/mL have been used. Other lab tests (eg C-reactive protein, erythrocyte sedimentation rate, serum iron, reticulocyte hemoglobin equivalent, sTfR, or TS) may be needed along with ferritin to diagnose iron-deficiency anemia in patients with inflammatory conditions.  

Ferritin testing is also useful in pregnant women who often present with elevated serum transferrin levels even in the absence of iron deficiency. This test has replaced bone marrow assessment of iron stores which was previously considered the gold standard for diagnosing 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.  

TS 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 TS.  

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.