Indications for Testing
Patients who present with anemia (Hb levels at least 2 standard deviations below the mean for age and sex) should be tested for iron deficiency.
Criteria for Diagnosis
The suggested diagnostic criteria for IDA are confirmed evidence of anemia and laboratory evidence of low iron stores.
The first recommended step in the evaluation of suspected IDA is a CBC, including an assessment of Hct, Hb, RBC count, platelet count, and white blood cell count, as well as a peripheral smear review to evaluate RBC morphology. RBC indices (including RBC distribution width [RDW]) from a CBC are particularly important for the initial evaluation of IDA. IDA is a microcytic anemia, but up to 40% of patients with IDA exhibit normocytic RBCs; thus, patients with anemia and an MCV of <95 fL should be tested for IDA. For patients with low Hb and an MCV ≥95 fL, consider testing for other types of anemia (see Anemia and Anemia Testing Algorithm).
Red Blood Cell Distribution Width
RDW, obtained from a CBC, will guide further testing. If RDW is high, iron studies (ferritin/iron and iron binding capacity) should be ordered. If RDW is normal, evaluate RBC count (from the CBC). In the case of an elevated RBC count, consider testing to distinguish between thalassemia and early iron deficiency. If the RBC count is low, consider evaluation for ACD/AI.
Ferritin/Iron and Iron Binding Capacity
SF and TIBC (which includes calculation of transferrin saturation) are the first-line tests to evaluate iron stores and can differentiate between IDA and other forms of microcytic anemia. Both IDA and ACD/AI exhibit low ferritin and low transferrin saturation. TIBC, however, is increased in severe IDA (although it may be normal in mild IDA), while it is decreased in ACD/AI. Iron levels vary throughout the day, so it is important to test iron during the morning, when iron levels are at their peak.
Hemoglobin A2 Quantification
An elevated RBC count with a reduced MCV raises clinical suspicion for thalassemia. HbA2 quantitation is suggested to distinguish between early iron deficiency and thalassemia (see Thalassemia topic). An elevated HbA2 level suggests possible thalassemia.
In certain cases, iron studies and HbA2 may be insufficient to evaluate a microcytic anemia.
Soluble Transferrin Receptor Test
Soluble transferrin receptor levels can be used to test for iron deficiency when other tests are nondiagnostic. Soluble transferrin receptor levels are increased in iron deficiency and are not affected by inflammation. It is important that soluble transferrin receptor test results be interpreted in the context of other iron status test results.
Erythrocyte Protoporphyrin Test
Erythrocyte protoporphyrin testing may be useful to distinguish between thalassemia minor and other causes of hypochromic microcytic anemia. Erythrocyte protoporphyrin levels are elevated in patients with iron deficiency, anemia of chronic disease, and sideroblastic anemia, but not in patients with thalassemia minor or other anemias associated with atypical heme synthesis.
Bone Marrow Biopsy
If IDA is not indicated by any of the above tests, but suspicion of IDA persists, a bone marrow biopsy may be considered to assess bone marrow iron levels. Although bone marrow biopsy is invasive, it remains the gold standard test for IDA. If bone marrow iron levels are low, the patient may be diagnosed with IDA; if not, additional testing may be required (see Anemia and Anemia Testing Algorithm).
Responsiveness to Oral Iron Treatment
An increase in Hb of 1 g/dL after 1 month of oral iron treatment confirms the diagnosis of IDA and indicates responsiveness to treatment. In patients who do not respond to oral iron supplementation, additional evaluation may be considered.
IDA is estimated to occur in <3% of the general United States population. No screening recommendation exists for asymptomatic adults. Although the U.S. Preventive Task Force finds insufficient evidence to recommend IDA screening during pregnancy, the American College of Obstetrics and Gynecology recommends universal Hb screening for pregnant women at an initial visit, and additional evaluation as appropriate.
Although the U.S. Preventive Task Force also finds insufficient evidence to recommend IDA screening in children, the American Academy of Pediatrics recommends universal Hb and risk factor screening for children at 1 year of age. If anemia (Hb <11 g/dL) is detected, additional screening, including SF and C-reactive protein (CRP), is recommended. Bright Futures (an initiative of the American Academy of Pediatrics) additionally recommends an anemia risk assessment at every visit, and annual screenings for infants and children up to 5 years of age who are at risk for IDA. Children 5-12 years and adolescent males 18-21 years should only be screened if risk factors are present. Females 12-21 years should be screened annually for anemia if risk factors are present, and every 5-10 years during routine health examinations.
In adults, IDA often results from chronic blood loss due to gastrointestinal or genitourinary bleeding (eg, menorrhagia). Identification and treatment of the source of bleeding are the first steps in the resolution of IDA related to blood loss; supplemental iron can then be provided to replenish iron stores. IDA related to decreased intake or absorption can also be treated with supplemental iron. In all patients receiving supplemental iron, an assessment of iron stores can be performed if Hb, Hct, and other RBC indices fail to respond to therapy as expected.
Patients without comorbidities on oral iron therapy should have Hb and RBC indices retested at 1 month to confirm the diagnosis of IDA and to evaluate the effectiveness of treatment. Thereafter, evaluation of Hb and iron stores is recommended every 3 months for the first year and once thereafter if Hb and RBC indices remain normal.
Patients on parenteral iron should have iron stores evaluated at 3 months following initiation of parenteral therapy and every 6 months thereafter until the cessation of therapy.
Patient Populations Requiring Special Consideration
Patients considering gastric bypass should be evaluated for IDA prior to surgery. Following surgery, patients who have had gastric bypass or another bariatric surgery are at increased risk for IDA due to reduced absorption of dietary iron. Evaluation of iron stores via SF and Tsat is recommended every 3 months following surgery for the first year. A complete iron workup to assess serum iron and iron stores is recommended every year following surgery. See Gastric Bypass topic for more information.
A complex inflammatory state exists in patients with chronic kidney disease, leading to challenges in iron homeostasis. Patients with chronic kidney disease should be tested for IDA every 3 months, or more often if receiving hemodialysis, intravenous iron, or an erythropoietin stimulating agent. Due to the increase in SF observed with inflammation, testing should include RBC indices and an assessment of iron stores using both Tsat and SF.
Anemia of inflammation is the most common complication of inflammatory bowel disease (IBD). Anemia is particularly complex in IBD, as IBD is a chronic inflammatory condition that also leads to problems with iron absorption, resulting in concomitant IDA. Furthermore, patients with IBD may also suffer from vitamin deficiencies, leading to simultaneous megaloblastic anemia. The European Crohn’s and Colitis Organization recommends assessing all patients with IBD for anemia with a CBC along with SF and CRP tests. Patients with mild IBD or IBD in remission should be tested every 6-12 months; patients with active disease should be tested every 3 months. Additionally, serum vitamin B12 and folate should be tested at least once per year. A full workup, including CBC, reticulocyte count, SF, Tsat, and CRP should be performed any time anemia is observed, and if needed, serum B12, folic acid, haptoglobin, reticulocyte hemoglobin, lactate dehydrogenase, soluble transferrin receptor, creatinine, and urea should be tested to identify the cause of anemia.