---

Medicines for Iron Deficiency Anemia (IDA)

1. ORAL IRON PREPARATIONS (First-line)

Dosing

---

Common Oral Iron Salts

Ferrous Sulfate (20% elemental iron) - Preferred / most cost-effective

• Tabs: 195 mg (39 mg Fe), 300 mg (60 mg Fe), 324 mg (65 mg Fe), 325 mg (65 mg Fe)
• Liquid: 75 mg/mL (15 mg Fe/mL)
• Adult dose per Rosen's Emergency Medicine: 325 mg PO TID (= 65 mg elemental Fe x3)
• Children: 2 mg/kg/day elemental iron orally

Ferrous Gluconate (11.6% elemental iron)

• Tabs: 240 mg (27 mg Fe), 324 mg (37.5 mg Fe)
• Preferred over ferrous sulfate in post-bariatric surgery patients as it does not require an acid medium for absorption (unlike ferrous sulfate)

Ferrous Fumarate (33% elemental iron) - Highest iron content per tablet

• Tabs: 90 mg (29.5 mg Fe), 324 mg (106 mg Fe), 325 mg (106 mg Fe), 456 mg (150 mg Fe)

Polysaccharide-Iron Complex / Ferrous Bis-glycinate Chelate

• Caps: 50 mg, 150 mg, 200 mg (expressed as elemental Fe)
• Less GI irritation; useful for patients intolerant to ferrous salts

---

Enhancers & Inhibitors of Absorption

Note: Take on an empty stomach for maximum absorption. Give with Vitamin C to improve bioavailability. If GI upset, can take with a small meal (reduces absorption by ~40%).

---

Common Side Effects

• Nausea, vomiting, epigastric pain
• Constipation
• Black/dark stools (warn the patient - not blood)
• Less GI irritation when taken with food or with non-sulfate formulations

---

Contraindications

• Hemolytic anemia
• Hemochromatosis
• GI tract inflammation (relative)

---

2. PARENTERAL (INTRAVENOUS) IRON

• Oral intolerance or malabsorption (e.g., celiac disease, short-bowel syndrome, post-gastrectomy)
• Chronic kidney disease (CKD) on dialysis
• Inflammatory bowel disease
• Post-partum IDA
• Patients on erythropoiesis-stimulating agents (ESA/EPO)
• Need for rapid repletion

---

IV Iron Formulations (Available in USA)

Safety Note (2025 evidence): A 2025 systematic review (PMID: 39935027) highlighted that ferric carboxymaltose is specifically associated with hypophosphatemia - monitor phosphate levels after infusion.

---

3. MONITORING TREATMENT RESPONSE

---

4. CAUSES OF TREATMENT FAILURE

• Poor compliance
• Insufficient dose
• Incorrect diagnosis (e.g., thalassemia, anemia of chronic disease)
• Ongoing blood loss not addressed
• Malabsorption

---

5. SPECIAL POPULATIONS

• Pregnancy: Ferrous sulfate 325 mg 2-3 times/day with Vitamin C, or parenteral iron if oral fails. Systematic review (PMID: 39163033) supports supplementation during pregnancy.
• Post-bariatric surgery: Prefer ferrous gluconate (doesn't need acid); avoid ferrous sulfate.
• CKD/dialysis: IV iron sucrose or ferric carboxymaltose preferred; oral poorly absorbed.
• Pediatrics: Ferrous sulfate drops/liquid at 3-6 mg elemental Fe/kg/day.

---

---

Iron Deficiency Anemia (IDA) - Complete Topic

---

1. DEFINITION & EPIDEMIOLOGY

• Affects ~10% of people in high-resource countries and 25-50% in low-resource countries
• Most prevalent in: toddlers, adolescent girls, and women of childbearing age
• Frequency in adult men and postmenopausal women: 2-5%

---

2. IRON METABOLISM (Background)

Normal Body Iron Distribution

Key Points

• Daily loss: 1-2 mg/day via shed mucosal and skin epithelial cells (no regulated excretion pathway)
• Daily diet contains 10-20 mg iron; 20% of heme iron is absorbed vs. only 1-2% of non-heme iron
• Iron transport in plasma: bound to transferrin (normally ~33% saturated)
  • Normal serum iron: ~120 µg/dL (men), ~100 µg/dL (women)
  • Normal TIBC: 300-350 µg/dL

Iron Absorption Pathway

1. Dietary ferric iron (Fe³⁺) reduced to ferrous (Fe²⁺) by duodenal cytochrome B (ferric reductase)
2. Transported across enterocyte apical membrane by DMT-1 (divalent metal transporter-1)
3. Exported from enterocyte basolateral membrane by ferroportin
4. Oxidized back to Fe³⁺ by hephaestin/ceruloplasmin - binds to transferrin

Hepcidin - The Master Regulator

• A small peptide secreted by the liver - negatively regulates ferroportin
• Iron levels sensed by HFE protein on hepatocytes → upregulates hepcidin → reduces absorption (feedback loop)
• Hepcidin is also upregulated by IL-6 (inflammation) - explains anemia of chronic disease
• Hepcidin is downregulated by erythroferrone (secreted by erythroblasts during increased erythropoiesis)
• In IDA: hepcidin levels fall (to maximize iron absorption)

---

3. ETIOLOGY / CAUSES

A. Chronic Blood Loss (Most common cause in high-resource countries)

• GI tract: Peptic ulcer, colon cancer, hemorrhoids, angiodysplasia, inflammatory bowel disease, hiatal hernia, Meckel's diverticulum, hookworm
• Gynecologic: Menorrhagia, metrorrhagia, fibroids, endometrial cancer
• Urinary: Hematuria (bladder/renal cancer, schistosomiasis)
• Pulmonary: Pulmonary hemosiderosis, severe hemoptysis
• Iatrogenic: Hemodialysis, frequent blood draws, surgical losses

B. Inadequate Intake (Most common in low-resource countries)

• Predominantly vegetarian/vegan diets (non-heme iron poorly absorbed)
• Malnutrition, poverty
• Infants fed exclusively milk
• Elderly with food insecurity

C. Increased Demands (Not met by normal diet)

• Pregnancy and breastfeeding
• Infancy and childhood (growth spurts)
• Adolescence
• Treatment with erythropoiesis-stimulating agents (EPO)

D. Malabsorption

• Celiac disease (most important - blunted duodenal villi)
• Helicobacter pylori gastritis (decreases absorption + microerosions)
• Atrophic/autoimmune gastritis (reduced acid - acid needed for Fe²⁺ conversion)
• Gastrectomy / Roux-en-Y gastric bypass (bypasses duodenum, main absorption site)
• Proton pump inhibitors (reduce acid needed for iron absorption)
• Excess tea, calcium, phytates in diet

---

4. STAGES OF IRON DEFICIENCY

---

5. PATHOPHYSIOLOGY

1. Iron stores are depleted first (ferritin falls, marrow iron disappears)
2. Serum iron falls, transferrin rises (body upregulates transferrin to capture every available iron atom)
3. Transferrin saturation drops below 15%
4. Hemoglobin synthesis becomes impaired → microcytic, hypochromic red cells
5. Additionally, iron-containing enzymes throughout the body are depleted → systemic effects (cognitive, immune, epithelial changes)
6. EPO rises in response to anemia, but marrow response is blunted by iron deficiency

---

6. CLINICAL FEATURES

General Anemia Symptoms (Nonspecific)

• Weakness, fatigue, listlessness
• Pallor (skin, conjunctivae, mucous membranes)
• Dyspnea on exertion
• Palpitations, tachycardia
• Reduced exercise tolerance
• Headache, dizziness

Specific Features of IDA (tissue iron depletion)

Plummer-Vinson Syndrome (Patterson-Kelly Syndrome)

1. Microcytic hypochromic anemia (IDA)
2. Post-cricoid esophageal webs (dysphagia)
3. Atrophic glossitis

---

7. PERIPHERAL BLOOD SMEAR MORPHOLOGY

Key Findings on Peripheral Smear

• Microcytes - small RBCs
• Hypochromia - enlarged zone of central pallor (normally 1/3 of cell diameter; in IDA pallor is >1/3, often leaving only a narrow peripheral rim of Hb)
• Pencil cells (cigar cells) - small, elongated RBCs (poikilocytosis)
• Anisocytosis - variation in cell size
• Increased RDW (red cell distribution width) - characteristic of IDA (distinguishes from thalassemia where RDW is normal)
• Thrombocytosis - platelet count often elevated (reactive)

Bone Marrow

• Mild to moderate increase in erythroid progenitors
• Absent stainable iron in macrophages on Prussian blue stain (diagnostically significant)

---

8. LABORATORY DIAGNOSIS

WHO Hemoglobin Cutoffs for Anemia

Complete Blood Count (CBC) in IDA

Iron Studies in IDA

Key diagnostic rule: Serum ferritin is the single best test for IDA in patients without chronic inflammatory disease. Ferritin < 15 ng/mL = 59% sensitivity, 99% specificity; ferritin cutoff < 41 ng/mL = 98% sensitivity and specificity.

Important: In chronic inflammation, ferritin is an acute phase reactant and may be falsely normal or elevated even in IDA - use sTfR/ferritin index or bone marrow in these cases.

---

9. DIFFERENTIAL DIAGNOSIS OF MICROCYTIC HYPOCHROMIC ANEMIA

---

10. EVALUATION APPROACH

Who Needs GI Workup?

• All adult men (regardless of age)
• All postmenopausal women
• Premenopausal women after excluding menorrhagia as the cause

GI Workup Sequence

1. Colonoscopy first (right-sided colon cancer is common cause)
2. Upper endoscopy + push enteroscopy if colonoscopy negative
3. Duodenal biopsy - for celiac disease
4. Test and treat H. pylori if found
5. Capsule endoscopy if all above negative
6. Investigate non-GI causes if capsule study negative

---

11. TREATMENT

A. Oral Iron (First-line)

• Take on empty stomach (food reduces absorption ~40%)
• Co-administer Vitamin C (ascorbic acid) - converts Fe³⁺ to Fe²⁺, enhances absorption
• Avoid with: antacids, calcium, tea, coffee, tetracyclines (mutual inhibition)

B. Parenteral (IV) Iron

• Oral intolerance or malabsorption (celiac, short-bowel, post-gastrectomy)
• Chronic kidney disease
• Inflammatory bowel disease
• Post-partum IDA
• Patients on ESA/EPO therapy
• Need for rapid repletion

Safety Alert (2025): A recent systematic review (PMID 39935027) confirmed ferric carboxymaltose is specifically associated with significant hypophosphatemia - monitor phosphate post-infusion.

C. Blood Transfusion

• Hb < 7 g/dL
• Hemodynamic instability / active bleeding
• Angina, syncope, severe dyspnea
• Cardiovascular compromise

D. Treat the Underlying Cause

---

12. MONITORING TREATMENT RESPONSE

Continue iron for at least 6 months total to fully replete stores even after Hb normalizes.

Causes of Treatment Failure

1. Poor compliance with medication
2. Insufficient dose
3. Incorrect diagnosis (e.g., thalassemia, ACD)
4. Ongoing blood loss not addressed
5. Malabsorption of oral iron
6. Mixed deficiency (concurrent B12/folate deficiency)

---

13. SPECIAL POPULATIONS

---

14. COMPLICATIONS OF UNTREATED IDA

• Impaired cognitive development in children (irreversible if prolonged)
• Reduced work capacity and productivity
• Impaired cell-mediated immunity - increased infection susceptibility
• Heart failure from severe chronic anemia
• Pica leading to ingestion of toxic substances
• Plummer-Vinson syndrome - risk of upper GI malignancy
• In pregnancy: preterm labor, low birth weight, maternal mortality

---

15. KEY EXAM POINTS (Summary)

---