Microcytic hypochromic anemia from depleted iron stores — most common anemia worldwide.
Also known as: IDA, iron deficiency, microcytic anemia, hypochromic anemia
Overview
Anemia resulting from insufficient body iron to sustain normal erythropoiesis. Defined by reduced hemoglobin with low ferritin (<30 ng/mL in most adults, <15 ng/mL highly specific) and reduced transferrin saturation (<20%).
Epidemiology
Most common cause of anemia globally and in the United States. Highest prevalence in menstruating women, pregnant patients, infants/toddlers, and adults with chronic blood loss. In men and postmenopausal women, GI blood loss must be excluded.
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Iron is required for heme synthesis. When demand exceeds supply (loss > absorption), storage iron (ferritin) is mobilized first, then transport iron (transferrin saturation falls), and finally functional iron in erythrocytes. Erythropoiesis becomes iron-restricted, producing small (microcytic), pale (hypochromic) red cells with reduced hemoglobin content.
Clinical presentation
Symptoms
Fatigue, dyspnea on exertion, exercise intolerance, lightheadedness
Headache, poor concentration, irritability
Pica (craving ice/pagophagia, clay, starch) — relatively specific for iron deficiency
Restless legs syndrome
Hair loss, brittle nails
Signs / physical exam
Pallor of conjunctiva, palms, nail beds
Tachycardia, systolic flow murmur
Koilonychia (spoon nails) — advanced/chronic
Angular cheilitis, atrophic glossitis (smooth red tongue)
Plummer-Vinson syndrome: dysphagia + esophageal web + IDA (rare, premalignant)
Classic findings
Pica with ice craving plus microcytic anemia and low ferritin is highly suggestive of iron deficiency.
Differential diagnosis
Anemia of chronic disease (ACD) — Ferritin normal or elevated (acute phase reactant), low TIBC, low transferrin saturation; iron sequestered by hepcidin
Thalassemia trait — Microcytosis disproportionate to mild anemia, normal RDW, Mentzer index <13 (MCV/RBC); hemoglobin electrophoresis abnormal in beta-thal
Sideroblastic anemia — Microcytic or dimorphic; ringed sideroblasts on marrow iron stain; elevated ferritin and iron
Lead poisoning — Basophilic stippling, occupational/environmental exposure, elevated blood lead level
Combined deficiency (B12/folate + iron) — Normocytic MCV with wide RDW; both micro- and macrocytic populations on smear
Diagnostic workup
Diagnostic criteria
Microcytic anemia (Hb low, MCV <80 fL) plus ferritin <30 ng/mL OR transferrin saturation <20% with consistent clinical context.
Iron studies — low ferritin (<30 ng/mL diagnostic in most adults; <100 ng/mL may indicate deficiency in inflammation/CKD), low serum iron, elevated TIBC, transferrin saturation <20%
Reticulocyte count — inappropriately low for degree of anemia
Soluble transferrin receptor — elevated in IDA, normal in ACD (useful when ferritin uninterpretable)
Stool occult blood; consider tissue transglutaminase IgA (celiac screen) in unexplained IDA
Imaging
Upper and lower endoscopy in men and postmenopausal women with IDA, and in premenopausal women not responding to iron
Capsule endoscopy if EGD/colonoscopy nondiagnostic and bleeding persists
Diagnostic algorithm
Parameter
Iron Deficiency
Anemia of Chronic Disease
Thalassemia Trait
MCV
Low
Normal or low
Low (disproportionate)
RDW
High
Normal
Normal
Ferritin
Low (<30)
Normal or high
Normal or high
Serum iron
Low
Low
Normal or high
TIBC
High
Low
Normal
Transferrin saturation
Low (<20%)
Low
Normal or high
sTfR
High
Normal
Normal or high
Iron studies pattern across the common microcytic anemias.
Treatment
First-line
Identify and correct the underlying cause (most important step)
Oral iron — ferrous sulfate 325 mg (65 mg elemental), ferrous gluconate, ferrous fumarate; one tablet every other day improves absorption and tolerability versus daily dosing
Take on empty stomach with vitamin C (orange juice) to enhance absorption; avoid concurrent calcium, antacids, PPIs, coffee, tea
Continue iron 3-6 months after hemoglobin normalizes to replete stores
Second-line / adjunct
IV iron — ferric carboxymaltose, iron sucrose, ferumoxytol, low-molecular-weight iron dextran; indicated for intolerance to oral iron, malabsorption (celiac, IBD, post-bypass), CKD on dialysis, ongoing blood loss exceeding oral absorption, or need for rapid replenishment (late pregnancy)
Transfusion reserved for hemodynamic instability, severe symptomatic anemia, or active hemorrhage
Complications
High-output heart failure (severe chronic anemia)
Impaired neurocognitive development in infants and young children
Worsened outcomes in HF, CKD, and post-operative recovery
Plummer-Vinson syndrome with risk of esophageal squamous cell carcinoma
PANCE pearls
Reticulocytosis should be visible within 7-10 days of starting oral iron; hemoglobin rises ~1 g/dL every 2-3 weeks.
Failure to respond to oral iron suggests ongoing loss, malabsorption, noncompliance, or wrong diagnosis (think thalassemia, ACD).
IV iron does NOT require a test dose for newer formulations (ferric carboxymaltose, ferumoxytol); anaphylaxis risk is much lower than with older high-molecular-weight iron dextran.
Ferritin is an acute phase reactant — can be falsely normal in inflammation, infection, malignancy, CKD. Use transferrin saturation and soluble transferrin receptor in these settings.
Every-other-day dosing minimizes hepcidin-driven absorption blockade and improves total iron uptake compared to daily dosing.
References
ASH 2020 — American Society of Hematology 2020 guidelines for management of iron deficiency anemia
AGA 2020 — AGA Clinical Practice Guidelines on the Gastrointestinal Evaluation of Iron Deficiency Anemia (Ko et al., Gastroenterology 2020)
WHO 2011 — WHO Hemoglobin concentrations for the diagnosis of anemia and assessment of severity
Stoffel et al. — Iron absorption from oral iron supplements given on consecutive versus alternate days (Lancet Haematology 2017)
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