Iron deficiency anemia (IDA)

Summary

Iron deficiency anemia (IDA) is the most common anemia worldwide and the most common cause of microcytic hypochromic anemia. It happens when iron stores drop below what the bone marrow needs to make hemoglobin — usually from chronic blood loss (GI in adult men/postmenopausal women, menstrual in women of reproductive age), poor intake (infants, vegans), malabsorption (celiac, post-gastrectomy), or increased demand (pregnancy, growth spurts).

Classic patient: a young woman with heavy periods, or an older adult with occult GI bleeding, who presents with fatigue, pallor, dyspnea on exertion, and sometimes pica, koilonychia (spoon nails), or angular cheilitis.

Labs show ↓Hb, ↓MCV, ↑RDW, ↓ferritin (most specific), ↓serum iron, ↑TIBC, and ↓transferrin saturation. Treatment is oral ferrous sulfate plus finding and correcting the source of iron loss — in adults >50, that means colonoscopy/endoscopy until proven otherwise.

Definition

Anemia caused by depleted total body iron, leading to insufficient iron for heme synthesis and resulting in microcytic (MCV < 80 fL), hypochromic red blood cells.

• Anemia = Hb < 13 g/dL in men, < 12 g/dL in non-pregnant women, < 11 g/dL in pregnancy/children.
• Iron deficiency can exist without anemia (latent stage) — ferritin is already low before Hb falls.

Epidemiology

• Most common anemia worldwide and the most common nutritional deficiency.
• Affects ~25% of the global population; rates much higher in developing countries.
• High-risk groups: women of reproductive age, pregnant women, infants & toddlers (6 mo – 2 yr), adolescents during growth spurts, and elderly with chronic GI blood loss.

Etiology

Four mechanisms cover every cause. Always think: where is the iron going, or why isn't it coming in?

Pathophysiology

Iron handling in one paragraph: dietary iron (heme > non-heme) is absorbed in the duodenum. Gastric acid converts Fe³⁺ → Fe²⁺ for absorption. Inside enterocytes, iron is either stored as ferritin or exported via ferroportin into blood, where it binds transferrin for delivery to bone marrow (heme synthesis) and tissues. Hepcidin from the liver blocks ferroportin — when body iron is low, hepcidin falls, allowing more absorption.

What happens in IDA:

• Iron loss/deficit > intake → storage iron (ferritin) depleted first.
• As stores fall, the body compensates by making more transferrin → ↑ TIBC, but with less iron to bind → ↓ transferrin saturation.
• Without enough iron, heme synthesis fails → erythrocytes are released small (microcytic) and pale (hypochromic).
• The marrow tries extra cell divisions to "use up" what little Hb is available → cells become even smaller.

Click here to view the hepcidin–ferroportin regulatory diagram.

Clinical Features

General anemia symptoms (any cause, from low Hb):

• Fatigue, weakness, decreased exercise tolerance
• Pallor (conjunctiva, palmar creases, nail beds)
• Dyspnea on exertion, tachycardia, palpitations
• Headache, dizziness, syncope

Specific to iron deficiency (high-yield — these point at IDA, not just any anemia):

• Koilonychia — spoon-shaped, brittle nails
• Angular cheilitis — cracks at corners of the mouth
• Atrophic glossitis — smooth, beefy red tongue
• Pica — craving non-food items (ice = pagophagia, dirt, clay, starch)
• Restless legs syndrome
• Plummer–Vinson syndrome (rare): IDA + esophageal web + dysphagia → ↑ risk of squamous cell esophageal carcinoma
• Children: irritability, poor school performance, developmental delay, breath-holding spells

Diagnosis

Step 1 — Complete blood count (CBC):

• ↓ Hb, ↓ MCV (microcytic, <80 fL), ↓ MCH/MCHC (hypochromic)
• ↑ RDW — often the earliest CBC clue (mixed cell sizes)
• Reticulocyte count low or inappropriately normal

Step 2 — Iron studies (confirm the diagnosis):

Step 3 — Peripheral blood smear: microcytic, hypochromic RBCs with marked central pallor, anisocytosis (varying sizes), poikilocytosis, and characteristic pencil (cigar) cells. View the classic IDA smear.

Step 4 — Find the cause (mandatory — never just "give iron"):

• Adult men & postmenopausal women → upper endoscopy + colonoscopy
• Premenopausal women → menstrual history; pelvic exam; if menses normal → consider GI workup
• Children → dietary history (cow's milk excess), screen for celiac if not responding
• If malabsorption suspected → anti-tissue transglutaminase (celiac), H. pylori testing

Differential Diagnosis

All microcytic anemias look similar on CBC — iron studies separate them. Remember TICS: Thalassemia, Iron deficiency, Chronic disease (late), Sideroblastic (and lead poisoning).

Quick differentiation pearls:

• IDA vs Thalassemia minor: RDW is high in IDA, normal in thalassemia. RBC count is low in IDA, normal/high in thalassemia. Mentzer index (MCV/RBC) > 13 → IDA; < 13 → thalassemia.
• IDA vs ACD: ferritin is the discriminator — low in IDA, high (or normal) in ACD. TIBC: high in IDA, low in ACD.
• View the full microcytic-anemia iron-studies comparison table.

Management

Two parallel tasks: (1) replace iron and (2) treat the underlying cause. Never give iron without investigating the source.

1. Oral iron — first-line

• Ferrous sulfate 325 mg PO once daily or every other day (every-other-day dosing improves absorption by lowering hepcidin response and reduces GI side effects).
• Other options: ferrous gluconate, ferrous fumarate (similar efficacy).
• Take on an empty stomach with vitamin C / orange juice (↑ absorption).
• Avoid co-administration with antacids, PPIs, calcium, tea, coffee, milk, or food rich in phytates (↓ absorption).
• Side effects: nausea, epigastric pain, constipation, black stools (harmless — warn the patient).
• Duration: continue iron for 3–6 months after Hb normalizes to refill stores (ferritin).

2. IV iron — when oral fails or is not possible

• Indications: oral intolerance, malabsorption (celiac, post-bariatric), chronic kidney disease on EPO, severe ongoing blood loss, IBD, or need for rapid correction (e.g., late pregnancy).
• Preparations: iron sucrose, ferric carboxymaltose, iron dextran (risk of anaphylaxis).

3. Blood transfusion

• Reserved for severe anemia with hemodynamic instability, active bleeding, or Hb < 7 g/dL with symptoms (lower threshold in cardiac disease).

4. Treat the underlying cause

• Stop NSAIDs, treat H. pylori, resect colon cancer, manage menorrhagia (OCPs, IUD, surgery), treat celiac (gluten-free diet), eradicate hookworm.

Complications

• High-output heart failure in severe, untreated anemia.
• Pregnancy: ↑ risk of preterm birth, low birth weight, and maternal mortality from peripartum hemorrhage.
• Children: impaired cognitive and motor development; poor school performance (may be irreversible if prolonged).
• Plummer–Vinson syndrome: chronic IDA + esophageal web + dysphagia → ↑ risk of esophageal squamous cell carcinoma.
• Restless legs syndrome and worsening of pre-existing cardiac/pulmonary disease.

Mnemonics

Key Points for Exams