How should I diagnose and manage iron‑deficiency anemia in an adult patient?

Iron Deficiency Anemia in Adults: Diagnosis and Management

Diagnose iron deficiency anemia by measuring serum ferritin (<30 ng/mL indicates deficiency in non-inflammatory states) and treat with oral ferrous sulfate 325 mg daily or on alternate days as first-line therapy, reserving intravenous iron for specific indications including oral intolerance, malabsorption, chronic inflammatory conditions, ongoing blood loss, or pregnancy. 1

Diagnostic Approach

Initial Testing

• Measure serum ferritin first when evaluating suspected iron deficiency or microcytosis (MCV <80 fL). 2, 1
• Low ferritin (<30 ng/mL) confirms iron deficiency in patients without inflammatory conditions. 1
• If ferritin is not low initially, proceed to measure transferrin saturation (TSAT), total iron-binding capacity (TIBC), and serum iron levels. 2
• Transferrin saturation <20% (calculated as serum iron/TIBC × 100) indicates iron deficiency, particularly useful when ferritin is equivocal. 1

Distinguishing from Other Conditions

• Anemia of chronic disease presents with low serum iron AND decreased TIBC (opposite pattern from iron deficiency, which shows elevated TIBC). 2
• Consider hemoglobin electrophoresis if thalassemia trait is suspected; beta-thalassemia trait shows elevated hemoglobin A2 levels. 2
• Serum transferrin receptor measurement can distinguish iron deficiency from anemia of chronic disease when both conditions coexist. 3

Identifying the Underlying Cause

• In adults, presume blood loss as the cause until proven otherwise, with gastrointestinal tract being the most common source. 2
• Gastrointestinal malignancy must be excluded in adults with new-onset iron deficiency anemia. 2
• Evaluate for heavy menstrual bleeding in reproductive-age women (38% have nonanemic iron deficiency, 13% have iron-deficiency anemia). 1
• Screen for malabsorption conditions: atrophic gastritis, celiac disease, post-bariatric surgery, and inflammatory bowel disease. 1
• Consider medication history, particularly NSAIDs and proton pump inhibitors. 1

Management Strategy

First-Line: Oral Iron Therapy

• Start with ferrous sulfate 325 mg daily or on alternate days for most patients. 1
• Alternate-day dosing may improve tolerability while maintaining efficacy. 1
• Calculate total iron deficit and plan treatment cycles of 5000 mg elemental iron over at least 1 month, with appropriate follow-up after each cycle. 4
• Continue therapy until iron stores are fully replenished, not just until hemoglobin normalizes. 5

Indications for Intravenous Iron

Switch to IV iron when oral therapy is inadequate or inappropriate: 1

• Oral iron intolerance or side effects
• Impaired absorption (celiac disease, post-bariatric surgery, atrophic gastritis)
• Chronic inflammatory conditions including chronic kidney disease, heart failure, inflammatory bowel disease, or cancer
• Ongoing blood loss that exceeds oral replacement capacity
• Second and third trimesters of pregnancy

Available IV formulations include iron dextran, iron gluconate, and iron sucrose. 3

Clinical Pitfalls to Avoid

• Do not rely on hemoglobin alone—it has low sensitivity and specificity for iron deficiency. 3
• Ferritin is an acute phase reactant; levels may be falsely normal or elevated in inflammatory states despite true iron deficiency. 1
• In chronic inflammatory conditions (CKD, HF, IBD), use transferrin saturation <20% as the diagnostic criterion rather than ferritin alone. 1
• Do not stop iron therapy when hemoglobin normalizes—continue until stores are replenished to prevent rapid recurrence. 5
• Failure to identify and address the underlying cause leads to treatment failure and recurrence. 2

Symptom Recognition

Iron deficiency causes symptoms even before anemia develops, including: 1

• Fatigue, irritability, depression, difficulty concentrating
• Restless legs syndrome (32-40% of iron-deficient patients)
• Pica (40-50% of cases)
• Dyspnea, lightheadedness, exercise intolerance
• Worsening heart failure symptoms in patients with existing cardiac disease