Anemia
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Iron Deficiency Anemia (IDA)
Iron deficiency is the most common nutritional disorder in the world and the leading cause of anemia globally. It affects ~10% of people in high-resource countries and 25–50% in low-resource settings.
Epidemiology & High-Risk Groups
- Toddlers and infants (low iron in breast milk: ~0.3 mg/L)
- Adolescent girls and premenopausal women (menstrual loss)
- Pregnant women (increased demand)
- Vegans (lack of heme iron)
- The elderly and impoverished
- Adult men and postmenopausal women with unexplained IDA → must be assumed to have GI blood loss until proven otherwise
Iron Metabolism (Key Concepts)
| Parameter | Males | Females |
|---|---|---|
| Total body iron | ~3.5 g | ~2.5 g |
| Hemoglobin compartment | 2100 mg | 1750 mg |
| Storage (ferritin + hemosiderin) | 1000 mg | 400 mg |
- Daily losses: 1–2 mg/day (shed epithelial cells); no regulated excretion pathway
- Daily requirement: ~7–10 mg (men), 7–20 mg (women)
- Dietary heme iron (from meat): ~20% absorbed; non-heme iron: only 1–2% absorbed
- Hepcidin (liver peptide) is the master regulator — it degrades ferroportin, suppressing iron absorption when stores are adequate; upregulated by IL-6 in inflammation (mechanism of anemia of chronic disease)
- Absorption enhancers: ascorbic acid, citric acid, amino acids
- Absorption inhibitors: tannins (tea), carbonates, oxalates, phosphates
— Robbins, Cotran & Kumar Pathologic Basis of Disease, p. 612; Robbins & Kumar Basic Pathology, p. 393
Causes
| Category | Examples |
|---|---|
| Dietary lack | Low-resource countries; vegans; infants; elderly |
| Impaired absorption | Celiac disease, sprue, gastrectomy, H. pylori infection, IBD (proximal small bowel) |
| Increased requirement | Pregnancy, infancy, adolescence |
| Chronic blood loss (most common in developed countries) | GI bleeding (cancer, ulcer, hookworm), menorrhagia, urinary tract loss |
In adult men and postmenopausal women in high-income countries, IDA must be attributed to GI blood loss until proven otherwise — an occult GI cancer may be the source.
— Robbins, Cotran & Kumar, p. 613
Pathophysiology (Stages of Depletion)
- Stage 1 – Pre-latent: Iron stores (ferritin) depleted; serum iron and Hb still normal; ↑ bone marrow erythroid activity
- Stage 2 – Latent iron deficiency: ↓ Serum iron and transferrin saturation; no anemia yet; ↑ TIBC
- Stage 3 – Iron deficiency anemia: Stores exhausted → ↓ Hb → microcytic, hypochromic anemia
Laboratory Findings
| Test | Iron Deficiency | Inflammation (ACD) | Thalassemia |
|---|---|---|---|
| Serum iron (µg/dL) | < 30 | < 50 | Normal–high |
| TIBC (µg/dL) | > 360 | < 300 | Normal |
| Transferrin saturation | < 10% | 10–20% | 30–80% |
| Ferritin (µg/L) | < 15 | 30–200 | 50–300 |
| Smear | Micro/hypo | Normal or mild micro/hypo | Micro/hypo + targeting |
— Harrison's Principles of Internal Medicine, 21st ed., p. 2889
Peripheral Blood Smear
Normal red cells (left) vs. iron deficiency anemia (right): cells are smaller (microcytic) with greatly increased central pallor (hypochromic). Poikilocytes (pencil cells, elliptocytes) may also be present.
Clinical Features
Symptoms of anemia:
- Fatigue, weakness, exertional dyspnea, pallor, palpitations
Signs specific to iron deficiency (severe/chronic):
- Koilonychia (spoon nails)
- Pica — craving for non-food items (ice = pagophagia, dirt = geophagia)
- Glossitis and angular stomatitis
- Plummer-Vinson syndrome — IDA + esophageal webs + dysphagia (rare)
- Restless leg syndrome association
Diagnosis
- CBC: ↓ Hb, ↓ MCV (microcytic), ↓ MCH (hypochromic), ↑ RDW
- Serum ferritin < 15 µg/L (most specific single test for depletion)
- ↓ Serum iron, ↑ TIBC, transferrin saturation < 10%
- Bone marrow: absent Prussian blue–stainable iron (gold standard, rarely needed)
- Reticulocyte response to iron therapy confirms diagnosis
GI evaluation (for adult men of any age and postmenopausal women):
- Colonoscopy first → upper endoscopy + push enteroscopy if negative → duodenal biopsy for celiac disease → test for H. pylori → capsule endoscopy if all negative
— Goldman-Cecil Medicine, p. 1424
Treatment
1. Oral Iron (First-line)
| Preparation | Tablet Size | Elemental Iron/Tablet | Usual Adult Dose (tablets/day) |
|---|---|---|---|
| Ferrous sulfate (hydrated) | 325 mg | 65 mg | 2–4 |
| Ferrous gluconate | 325 mg | 36 mg | 3–4 |
| Ferrous fumarate | 325 mg | 106 mg | 2–3 |
Key points:
- Ferrous (Fe²⁺) salts are absorbed ~3× better than ferric (Fe³⁺) salts
- Optimal dose: 150–200 mg elemental iron/day; once-daily dosing on an empty stomach may maximize absorption by avoiding hepcidin-mediated suppression from multiple daily doses
- Continue for 3–6 months after Hb normalizes to replenish stores
- Ascorbic acid (≥200 mg) co-administration increases absorption by ~30%
- Take separately from antacids, dairy, tea, and calcium supplements
- Hb should rise ~1–2 g/dL per week with adequate therapy; reticulocytosis peaks at 7–10 days
Side effects (dose-related): nausea, epigastric discomfort, constipation/diarrhea, black stools (no clinical significance)
— Katzung's Basic & Clinical Pharmacology, 16th ed., p. 932; Goodman & Gilman's Pharmacological Basis of Therapeutics, p. 929
2. Parenteral Iron (Reserved for specific indications)
Indications: intolerance/malabsorption of oral iron, hemodialysis patients on erythropoietin, inflammatory bowel disease involving proximal small bowel, post-gastrectomy, rapid repletion needed.
Available agents:
- Iron dextran — IV or IM; test dose required (anaphylaxis risk)
- Sodium ferric gluconate complex — lower anaphylaxis risk
- Iron sucrose — well tolerated, widely used in renal patients
- Ferric carboxymaltose / ferumoxytol — newer agents, high-dose single infusions possible
3. Blood Transfusion
Reserved for severe symptomatic anemia (Hb < 7–8 g/dL with hemodynamic compromise) or urgent pre-operative correction.
Summary: IDA at a Glance
| Feature | Detail |
|---|---|
| Most common cause (developed world) | Chronic GI blood loss |
| Most common cause (globally) | Dietary insufficiency |
| Most specific lab test | Serum ferritin < 15 µg/L |
| Smear morphology | Microcytic, hypochromic; pencil cells, poikilocytes |
| First-line treatment | Oral ferrous sulfate 325 mg once daily |
| Treatment duration | 3–6 months after Hb correction |
| Must exclude in adult men/postmenopausal women | GI malignancy |
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