Iron Deficiency Anemia
The combination of high total iron-binding capacity (TIBC), low serum iron, and low transferrin saturation is diagnostic of iron deficiency anemia, and you should initiate oral ferrous sulfate 200 mg twice daily for 4 weeks while simultaneously investigating the underlying cause of iron loss. 1
Diagnostic Interpretation
Elevated TIBC reflects the body's compensatory attempt to mobilize all available iron stores to maintain erythropoiesis, and this elevation may occur before serum iron drops, representing an early marker of developing iron deficiency. 2
Low serum iron (<70 μg/dL in men, <60 μg/dL in women) combined with low transferrin saturation (<20%) confirms inadequate circulating iron available for red blood cell production. 1, 3
Serum ferritin must be checked to distinguish absolute iron deficiency (ferritin <30 μg/L without inflammation, or <100 μg/L with inflammation) from functional iron deficiency (normal or elevated ferritin with low TSAT). 4
If ferritin is normal or elevated despite low TSAT, check C-reactive protein (CRP) or erythrocyte sedimentation rate (ESR) to identify inflammation-driven hepcidin upregulation that blocks iron release from stores. 1, 4
Underlying Cause Investigation
You must identify the source of iron loss or malabsorption before assuming treatment alone will suffice. 4
In premenopausal women, obtain detailed menstrual history to quantify blood loss; if menorrhagia is present, urgent gynecologic consultation is essential because iron replacement will fail without controlling the bleeding source. 5
In men and postmenopausal women, gastrointestinal blood loss is the most common cause—perform fecal occult blood testing and proceed to bidirectional endoscopy (colonoscopy first if age >50 years) to exclude malignancy. 4, 6
Screen for celiac disease with tissue transglutaminase antibodies, test for Helicobacter pylori, and review dietary intake to identify malabsorption or inadequate intake. 4
Assess renal function (serum creatinine, estimated glomerular filtration rate) because chronic kidney disease commonly causes functional iron deficiency and alters iron metabolism. 1, 7
Treatment Approach
Start oral ferrous sulfate 200 mg twice daily for 4 weeks; alternative formulations include ferrous fumarate or ferrous gluconate if ferrous sulfate is not tolerated. 1
Recheck complete blood count and iron studies at 8–10 weeks after initiating treatment—expect a hemoglobin rise of 1–2 g/dL if the patient is responding. 1, 6
If hemoglobin does not increase by ≥1 g/dL at 1 month, consider malabsorption of oral iron, ongoing blood loss, or an undiagnosed lesion, and transition to intravenous iron. 1, 5
Responders should continue oral iron for 3 months total after hemoglobin correction to replenish iron stores. 1
Intravenous iron options—ferric carboxymaltose 750 mg IV on day 1, repeated after 7 days (total 1500 mg)—are first-line for severe anemia (hemoglobin <7 g/dL) or oral iron failure. 1, 5
Monitoring and Target Goals
Target hemoglobin >11–12 g/dL, transferrin saturation >20%, and ferritin 100–800 ng/mL, depending on the underlying condition. 1
Do not recheck ferritin immediately after IV iron because it will be falsely elevated; wait 8–10 weeks for accurate assessment. 1
Monitor hemoglobin every 3 months for the first year after treatment, then annually, to ensure long-term stability. 5
Critical Pitfalls to Avoid
Do not rely on ferritin alone in the presence of inflammation (elevated CRP/ESR)—ferritin is an acute-phase reactant and may be falsely normal or elevated despite true iron deficiency. 4, 7
Do not start iron therapy before obtaining baseline iron studies, as this will obscure the diagnosis and delay identification of the underlying cause. 4
Do not miss thalassemia trait—if mean corpuscular volume (MCV) is markedly low (<70 fL) with normal or high ferritin and normal or high TSAT, order hemoglobin electrophoresis to exclude thalassemia before treating with iron. 4
Do not overlook gastrointestinal malignancy in men and postmenopausal women—9% of patients older than 65 years with iron deficiency anemia have gastrointestinal cancer when evaluated. 4, 6