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"iron deficiency anemia"[MeSH Terms] AND treatment

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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 is particularly prevalent in toddlers, adolescent girls, women of childbearing age, and people in low-resource settings.

Normal Iron Metabolism

Understanding IDA starts with iron homeostasis:

Iron metabolism cycle - Robbins Pathology

Fig. 14.20 – Iron is absorbed in the duodenum, bound to plasma transferrin, delivered to bone marrow erythroid precursors, incorporated into hemoglobin, and recycled when RBCs are destroyed by macrophages (spleen, liver, marrow). Daily loss is 1-2 mg via shed epithelial cells and endometrium.

Key numbers:

Parameter	Males	Females
Total body iron	~3,450 mg	~2,450 mg
Iron in hemoglobin	2,100 mg	1,750 mg
Storage iron (ferritin/hemosiderin)	1,000 mg	400 mg
Daily dietary requirement	7-10 mg	7-20 mg

Normal diet in the US contains 10-20 mg/day; ~20% of heme iron is absorbed vs. only 1-2% of nonheme iron.
Iron is transported in plasma by transferrin (normally ~1/3 saturated, serum iron ~100-120 µg/dL).
Hepcidin (liver-derived peptide) is the master regulator: it binds ferroportin on enterocytes and macrophages, promoting its degradation, thus reducing iron absorption and release. Low iron stores → low hepcidin → more absorption. Inflammation → high hepcidin → iron sequestration (basis of anemia of chronic disease).

Causes / Etiology

IDA develops from one of four mechanisms:

1. Dietary Lack

Rare in high-resource countries (most dietary iron is heme-iron from meat)
Common in infants (breast milk provides only ~0.3 mg/L iron), impoverished individuals, older adults with restricted diets, and vegans

2. Impaired Absorption

Celiac disease, sprue, other malabsorption syndromes
Post-gastrectomy (reduced acidity in proximal duodenum; faster transit)
Dietary inhibitors: tannins (tea), carbonates, oxalates, phosphates
Dietary enhancers: ascorbic acid, citric acid, amino acids

3. Increased Requirement

Infants, children, and adolescents during growth spurts
Pregnancy and menstruation
Women in low-resource countries with multiple, closely-spaced pregnancies

4. Chronic Blood Loss (most common cause in developed countries)

GI bleeding: peptic ulcer, colorectal cancer, angiodysplasia, hookworm
Gynecologic: menorrhagia
Urinary tract bleeding (less common)
Iron deficiency in an adult male or postmenopausal female must be attributed to GI blood loss until proven otherwise - missing a GI cancer here can be a fatal error.

Stages of Iron Deficiency

Iron deficiency progresses through three sequential stages:

Stage	Storage Iron	Serum Iron / Transferrin Sat	Hemoglobin / Hematocrit	Bone Marrow
Pre-latent (depletion)	↓↓	Normal	Normal	Absent stainable iron
Latent (iron-deficient erythropoiesis)	Absent	↓ serum Fe; ↑ TIBC; Sat <15%	Normal	Erythroid hyperplasia
IDA (overt anemia)	Absent	↓↓ serum Fe; ↓↓ ferritin; ↑ TIBC	↓ Hgb + ↓ Hct	Hypochromic microcytic cells

Morphology / Blood Smear

IDA peripheral blood smear - Robbins Pathology

Fig. 14.22 – IDA blood smear: hypochromic microcytic red cells with a narrow rim of peripheral hemoglobin (enlarged central pallor >1/3 of cell diameter). "Pencil cells" (elongated poikilocytes) are characteristic. The darker, well-hemoglobinized cells visible here are from a recent transfusion.

Bone marrow findings:

Mild to moderate increase in erythroid progenitors
Absent stainable iron in macrophages on Prussian blue stain - this is the gold standard diagnostic finding

Laboratory Findings

Test	Finding in IDA
Hemoglobin / Hematocrit	↓
MCV	↓ (microcytic)
MCH / MCHC	↓ (hypochromic)
Serum iron	↓
Serum ferritin	↓ (<12 µg/L) - most sensitive early marker
TIBC (transferrin)	↑
Transferrin saturation	↓ (<15%)
Serum hepcidin	↓ (reduced stores inhibit synthesis)
Blood smear	Microcytic, hypochromic; pencil cells
Reticulocyte count	Low (or normal)

Note: Ferritin is an acute-phase reactant. In concurrent inflammation, ferritin can be falsely normal even with true iron deficiency (overlap with anemia of chronic disease).

Clinical Features

General anemia symptoms (non-specific):

Fatigue, pallor, exertional dyspnea, palpitations, headache, dizziness

Features specific to severe / longstanding IDA (from iron depletion in non-hematopoietic tissues):

Koilonychia - spoon-shaped nails
Alopecia - hair loss
Atrophic glossitis - smooth, sore tongue
Angular cheilitis - cracking at corners of mouth
Pica - craving for non-food items (clay, ice = pagophagia, flour)
Plummer-Vinson syndrome (rare triad): microcytic hypochromic anemia + atrophic glossitis + esophageal webs
Gastric mucosal atrophy; intestinal malabsorption

Investigation Approach

For adult men and postmenopausal women with IDA, GI evaluation is mandatory:

Colonoscopy first (most common source is colorectal carcinoma or angiodysplasia)
Upper endoscopy + push enteroscopy if colonoscopy negative
Duodenal biopsy to exclude celiac disease
Treat H. pylori if found (decreases iron absorption; causes microerosions)
Capsule endoscopy if all three above are unrevealing
If capsule study negative → investigate non-GI causes

(Goldman-Cecil Medicine, Chapter 145)

Treatment

Oral Iron

First-line for most patients
Ferrous sulfate 325 mg (65 mg elemental iron) three times daily
Reticulocyte count rises in 5-7 days after starting iron
Hemoglobin normalizes over weeks; continue for 3-6 months after normalization to replenish stores
Side effects: constipation, nausea, dark stools (reduce adherence)
Take on empty stomach for better absorption; ascorbic acid helps; avoid antacids, tea, dairy within 1-2 hours

IV Iron

Indicated when oral iron is not tolerated, malabsorption is present, ongoing blood loss exceeds oral replacement capacity, or rapid repletion is needed (perioperative, heart failure, IBD)
Agents: ferric carboxymaltose, iron sucrose, ferumoxytol, low-molecular-weight iron dextran

Treat the Underlying Cause

This is as important as iron replacement. IDA that is not explained must prompt a search for occult GI malignancy.

IDA vs. Anemia of Chronic Disease (ACD) - Key Distinction

Feature	IDA	ACD
Serum iron	↓	↓
TIBC	↑	↓ or normal
Ferritin	↓	Normal or ↑
Hepcidin	↓	↑
Marrow iron	Absent	Present (increased)

Recent Evidence (2024-2025)

The AGA Clinical Practice Update on IDA (2024) provides updated guidance on GI workup. A 2025 Lancet Haematology consensus statement by Benson et al. addresses evidence-based management across children, adults, and pregnant individuals - including updated IV iron indications and dosing.

Sources:

Robbins, Cotran & Kumar Pathologic Basis of Disease, pp. 612-615
Goldman-Cecil Medicine, Chapter 145
DeLoughery TG et al. AGA Clinical Practice Update on IDA, 2024. Clin Gastroenterol Hepatol.
Benson AE et al. Management of iron deficiency, Lancet Haematol 2025.

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