What is the diagnosis and treatment approach for iron deficiency anemia in various patient populations, including women of childbearing age, pediatric populations, and those with gastrointestinal disorders?

Iron Deficiency Anemia: Diagnosis and Treatment

Diagnostic Approach

Diagnose iron deficiency anemia using a ferritin cutoff of <45 ng/mL rather than the traditional <15 ng/mL threshold, as this provides superior diagnostic accuracy. 1

Initial Laboratory Testing

• Obtain hemoglobin/hematocrit and serum ferritin as first-line tests 1
• Define anemia as hemoglobin below the lower limit of normal for age and sex:
  • Premenopausal women and adolescent girls (12-18 years): <12.0 g/dL 1, 2
  • Postmenopausal women and men: age-specific thresholds 1
• Ferritin <45 ng/mL confirms iron deficiency in anemic patients 1
• Consider transferrin saturation if ferritin is equivocal or inflammation is suspected 1

Therapeutic Diagnosis

• A hemoglobin rise ≥10 g/L (≥1 g/dL) within 2-4 weeks of iron therapy strongly confirms iron deficiency, even with equivocal iron studies 1, 3, 2

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Investigation for Underlying Cause

Men and Postmenopausal Women

All men and postmenopausal women with unexplained iron deficiency anemia require urgent bidirectional endoscopy (upper and lower GI) because approximately one-third have underlying GI pathology, including malignancy. 1

• This is a strong recommendation given the high risk of missing GI cancer 1
• Bidirectional endoscopy should be performed even in asymptomatic patients 1

Premenopausal Women

Premenopausal women with iron deficiency anemia should undergo bidirectional endoscopy, though this is a conditional recommendation given the lower pretest probability of serious pathology. 1

• Young women with obvious alternative explanations (heavy menstrual bleeding, dietary insufficiency) may reasonably defer endoscopy initially 1
• However, do not assume menstruation explains the anemia without considering GI pathology 1

Additional Testing

• Test for celiac disease with serologic testing (tissue transglutaminase IgA plus total IgA) first; only perform small bowel biopsy if serology is positive 1
• Consider non-invasive H. pylori testing, with treatment if positive 1
• Avoid routine gastric biopsies for atrophic gastritis 1
• Reserve capsule endoscopy for refractory or recurrent IDA after negative bidirectional endoscopy, particularly in patients on anticoagulation or with comorbidities 1

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Treatment: Iron Replacement Therapy

Oral Iron Therapy (First-Line)

Prescribe oral elemental iron with population-specific dosing:

Adults (General Population)

• 100-200 mg elemental iron daily 1
• Administer between meals or on empty stomach to maximize absorption 4
• If GI side effects occur, take with meals (despite reduced absorption) or try alternative formulations (ferrous gluconate, ferrous fumarate) 4
• Add vitamin C to enhance absorption 4

Adolescent Girls (12-18 years) and Nonpregnant Women of Childbearing Age

• 60-120 mg elemental iron daily 1, 4, 3
• Provide dietary counseling emphasizing iron-rich foods and vitamin C co-ingestion 1, 4
• Screen annually if risk factors present (heavy menstrual bleeding, low dietary iron, restrictive diets) 1, 4

Adolescent Boys (12-18 years)

• 120 mg elemental iron daily (two 60-mg tablets) 3
• Only screen if history of iron deficiency anemia, special healthcare needs, or documented low iron intake 3

Pregnant Women

• 30 mg elemental iron daily starting at first prenatal visit for prevention 1
• If anemia develops (Hb <11 g/dL first/third trimester or <10.5 g/dL second trimester), increase to 60-120 mg daily for treatment 1

Monitoring and Duration

• Recheck hemoglobin after 4 weeks of treatment 1, 4, 3, 2
• Expected response: hemoglobin increase ≥1 g/dL 3, 2
• If response confirmed, continue iron for an additional 2-3 months after hemoglobin normalizes to replenish iron stores 1, 4, 3, 2
• Total treatment duration typically 3-6 months 3
• Reassess hemoglobin approximately 6 months after treatment completion 1, 2

When Oral Iron Fails

If no response after 4 weeks despite compliance and absence of acute illness, obtain additional testing (MCV, RDW, serum ferritin) to evaluate for alternative diagnoses 1, 3, 2

• Consider thalassemia minor or sickle cell trait in patients of African, Mediterranean, or Southeast Asian ancestry with persistent microcytic anemia unresponsive to iron 1, 3

Intravenous Iron Therapy

Reserve IV iron for specific indications; it should not be first-line therapy 4

Indications for IV iron:

• Intolerance to at least two different oral iron preparations 4
• Documented non-compliance with oral therapy 4
• Conditions with compromised GI absorption (inflammatory bowel disease with active inflammation, celiac disease, post-bariatric surgery) 4
• Severe anemia requiring rapid correction 1

Important caveat: IV iron is more expensive, carries risk of anaphylaxis, and does not produce faster hemoglobin rise than oral iron in most cases 4

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Common Pitfalls to Avoid

• Do not discontinue iron therapy as soon as hemoglobin normalizes—stores must be replenished over 2-3 additional months 1, 4, 3, 2
• Do not assume all microcytic anemia is iron deficiency—consider thalassemia trait in at-risk populations 1, 3
• Do not skip GI investigation in men and postmenopausal women—one-third have significant GI pathology 1
• Do not use IV iron as first-line therapy—oral iron is equally effective in most cases and safer 4
• Do not perform routine gastric biopsies or capsule endoscopy without specific indications 1