What is the standard workup for iron deficiency anemia?

Standard Workup for Iron Deficiency Anemia

The standard workup for iron deficiency anemia requires confirming both anemia and iron deficiency through laboratory testing, followed by investigation of the underlying cause through gastrointestinal evaluation and screening for malabsorption disorders. 1

Initial Laboratory Confirmation

Define Anemia

• Hemoglobin below the lower limit of normal for your laboratory (typically <13 g/dL in men, <12 g/dL in non-pregnant women) 1
• Any level of anemia warrants investigation when iron deficiency is present, though more severe anemia increases likelihood of serious pathology 1

Confirm Iron Deficiency

Serum ferritin is the single most powerful test for iron deficiency: 1

• Ferritin <15 μg/L is diagnostic (specificity 0.99) 1
• Ferritin <45 μg/L provides optimal sensitivity/specificity balance and should prompt investigation 1
• Ferritin 45-100 μg/L may indicate iron deficiency in inflammatory conditions; add transferrin saturation <20% to confirm 1, 2
• Ferritin >100-150 μg/L essentially excludes absolute iron deficiency 1

Additional Red Cell Parameters

• Mean corpuscular volume (MCV) and mean corpuscular hemoglobin (MCH) detect microcytosis and hypochromia 1
• MCH may be more reliable than MCV as it's less machine-dependent 1
• Red cell distribution width (RDW) helps identify combined deficiencies 1
• Reticulocyte count distinguishes inadequate production from hemolysis 1

Minimum Workup Panel

Order these tests initially: 1

• Complete blood count with red cell indices (MCV, MCH, RDW)
• Serum ferritin
• Transferrin saturation
• C-reactive protein (CRP) to assess for inflammation
• Reticulocyte count

Investigation of Underlying Cause

Non-Invasive Screening (Perform First)

Screen for these common causes before endoscopy: 1

1. Celiac disease serology (tissue transglutaminase IgA with total IgA level) - found in 3-5% of IDA cases 1
2. Helicobacter pylori testing (non-invasive stool antigen or urea breath test) 1
3. Urinalysis or urine microscopy to exclude urinary blood loss 1

Gastrointestinal Endoscopy

Bidirectional endoscopy (gastroscopy AND colonoscopy) is indicated for: 1

• All men with confirmed IDA
• All postmenopausal women with confirmed IDA
• Premenopausal women with IDA who:
  • Are older (especially >40 years) 3
  • Have gastrointestinal symptoms
  • Have family history of GI malignancy
  • Fail to respond to iron therapy
  • Have no obvious gynecological cause

Key endoscopy principles: 1

• Perform both upper and lower endoscopy even if one reveals pathology (unless advanced gastric cancer or confirmed celiac disease found)
• Colonoscopy is preferred over CT colonography, but either is acceptable if colonoscopy unavailable 1
• Avoid routine biopsies for celiac disease unless serology positive or endoscopic abnormality present 1
• Reserve H. pylori biopsies for those with endoscopic abnormality and negative non-invasive testing 1

When to Investigate Small Bowel

Small bowel investigation (capsule endoscopy, CT/MR enterography) is NOT routine after negative bidirectional endoscopy 1, 3

Proceed to small bowel evaluation if: 1, 3

• Inadequate response to iron replacement therapy
• Recurrent IDA after initial correction
• Red flag symptoms (weight loss, abdominal pain, elevated CRP)
• Patients requiring anticoagulation with unrevealing bidirectional endoscopy 1

Special Considerations

Hemoglobinopathy Screening

• Obtain hemoglobin electrophoresis in patients with microcytosis and normal iron studies, particularly those of appropriate ethnic background (Mediterranean, African, Southeast Asian descent) 1
• This prevents unnecessary GI investigation when thalassemia is the cause 1

Premenopausal Women

• Women <40 years with obvious menstrual blood loss may receive empiric iron therapy first 1
• Endoscopy can be deferred if hemoglobin normalizes and remains stable with iron replacement
• Lower threshold for investigation if family history of GI cancer, persistent symptoms, or failure to respond to therapy 1

Response to Iron Therapy as Diagnostic Tool

• Hemoglobin rise ≥10 g/L within 2 weeks strongly suggests absolute iron deficiency, even with equivocal iron studies 1
• This can help confirm diagnosis when ferritin interpretation is unclear due to inflammation

Common Pitfalls to Avoid

Do not assume dietary insufficiency is the cause - even with positive dietary history, complete GI investigation is required in at-risk populations 1

Do not use fecal occult blood testing - it has no benefit in IDA workup and should not be performed 1

Do not stop at finding one cause - complete bidirectional endoscopy even if upper GI pathology found, unless advanced malignancy or celiac disease confirmed 1

Do not delay investigation based on arbitrary hemoglobin cutoffs - investigate any level of anemia with confirmed iron deficiency, particularly in men and postmenopausal women 1