What is the framework for diagnosing and treating iron deficiency anemia and monitoring for appropriate treatment response?

Framework for Diagnosing and Treating Iron Deficiency Anemia

Diagnosis

Iron deficiency anemia should be diagnosed using hemoglobin concentration combined with iron studies (serum ferritin and transferrin saturation), with diagnostic thresholds adjusted based on the presence of inflammation.

Initial Laboratory Assessment

• Obtain complete blood count with mean corpuscular volume (MCV), reticulocyte count, serum ferritin, transferrin saturation (TSAT), and C-reactive protein (CRP) as the minimum workup 1
• Hemoglobin concentration is more sensitive than hematocrit for detecting anemia 2
• MCV <76 fL suggests iron deficiency, though normal MCV does not exclude it 1

Defining Iron Deficiency

Without inflammation:

• Serum ferritin <30 μg/L confirms iron deficiency 1
• TSAT <20% supports the diagnosis 1

With inflammation (elevated CRP or clinical evidence):

• Serum ferritin up to 100 μg/L may still indicate iron deficiency 1
• Ferritin 30-100 μg/L with TSAT <20% suggests combined true iron deficiency and anemia of chronic disease 1
• Ferritin >100 μg/L with TSAT <20% indicates functional iron deficiency 1

Identifying the Underlying Cause

• Perform upper gastrointestinal endoscopy with small bowel biopsies (to exclude celiac disease, present in 2-3% of cases) 1
• Conduct colonoscopy or double-contrast barium enema, as dual pathology occurs in 10-15% of patients 1
• Check for celiac disease with transglutaminase antibody (IgA) and total IgA 3
• Exclude urinary tract bleeding by checking for hematuria 1
• In premenopausal women <40-45 years with obvious menstrual causes, bidirectional endoscopy may be deferred 1, 3

Treatment

All patients with iron deficiency anemia should receive iron supplementation to normalize hemoglobin and replenish iron stores, with intravenous iron preferred over oral iron in patients with active inflammatory bowel disease, previous oral iron intolerance, hemoglobin <10 g/dL, or when rapid response is needed.

Oral Iron Therapy

• First-line for stable patients: Ferrous sulfate 200 mg (65 mg elemental iron) three times daily 1, 4
• Alternative formulations: ferrous gluconate or ferrous fumarate are equally effective 1
• For children: 3 mg/kg/day of elemental iron administered between meals 2
• Administer between meals to maximize absorption 1, 2
• Add ascorbic acid (vitamin C) to enhance absorption if response is poor 1, 2
• Lower doses (28-50 mg elemental iron daily) may improve compliance by reducing gastrointestinal side effects 5

Intravenous Iron Therapy

Indications for IV iron as first-line treatment:

• Clinically active inflammatory bowel disease 1
• Previous intolerance to at least two oral iron preparations 1
• Hemoglobin <10 g/dL 1
• Intestinal malabsorption (celiac disease, atrophic gastritis, post-bariatric surgery) 3
• Need for erythropoiesis-stimulating agents 1
• Functional iron deficiency (TSAT 20-50%, ferritin 30-800 ng/mL) 1

Dosing:

• Simple dosing scheme: 1000 mg total iron dose for most patients with hemoglobin ≥7 g/dL 1
• For hemoglobin <7 g/dL, consider additional 500 mg 1
• Available formulations include ferric carboxymaltose, iron sucrose, and iron isomaltoside 1

Blood Transfusion

• Reserve for severe, symptomatic anemia with hemodynamic instability 2, 6
• Hemoglobin <7 g/dL in unstable patients warrants consideration 2

Monitoring Treatment Response

An increase in hemoglobin of ≥2 g/dL (or ≥1 g/dL in children) after 3-4 weeks confirms appropriate response and iron deficiency as the diagnosis.

Initial Response Assessment

• Recheck hemoglobin after 3-4 weeks of treatment 1
• Expected rise: ≥2 g/dL in adults 1 or ≥1 g/dL in children 2
• In children, hematocrit should increase ≥3% 2

Failure to Respond

If hemoglobin fails to rise appropriately, consider:

• Poor compliance (most common cause) 1
• Continued blood loss 1
• Malabsorption 1
• Misdiagnosis 1
• Concomitant vitamin B12 or folate deficiency 1

Duration of Treatment

• Continue iron for 3 months after hemoglobin normalization to replenish iron stores 1
• In children, continue for 2 additional months after confirmation of response 2

Long-Term Monitoring

• Monitor hemoglobin and MCV at 3-month intervals for one year, then annually 1
• Check ferritin if hemoglobin or MCV falls below normal 1
• For patients with recurrent deficiency, consider intermittent oral supplementation every 6-12 months 5
• Further investigation is only necessary if hemoglobin cannot be maintained with iron supplementation 1

Common Pitfalls

• Do not rely on faecal occult blood testing—it is insensitive and non-specific 1
• Do not accept upper GI lesions alone (esophagitis, erosions, peptic ulcer) as the cause without also investigating the colon, as dual pathology occurs in 10-15% 1
• Avoid long-term iron supplementation when ferritin is normal or elevated, as this is potentially harmful 5
• Do not use serum ferritin alone in the presence of inflammation; it acts as an acute phase reactant and may be falsely elevated 1
• Recognize that normal MCV does not exclude iron deficiency, especially when microcytosis and macrocytosis coexist 1