What are the recommended diagnostic steps for iron deficiency anemia in a patient with potential risk factors such as heavy menstrual bleeding or gastrointestinal disorders?

Diagnosis of Iron Deficiency Anemia

Begin with a complete blood count and serum ferritin level—a ferritin <45 ng/mL confirms iron deficiency with optimal sensitivity, while ferritin <12 μg/dL is diagnostic of absolute iron deficiency. 1

Initial Laboratory Evaluation

Essential First-Line Tests

• Complete Blood Count (CBC): Measure hemoglobin (preferred over hematocrit due to better reproducibility), mean corpuscular volume (MCV), and red cell distribution width (RDW) 1

  • Hemoglobin below the laboratory's lower limit of normal defines anemia (typically <11.5 g/dL for women, <13.8 g/dL for men) 1
  • Microcytosis (low MCV) is characteristic but may be absent in combined deficiencies 1
  • Elevated RDW suggests combined iron and folate deficiency 1

• Serum Ferritin: The most powerful single test for iron deficiency 1

  • <12 μg/dL is diagnostic of absolute iron deficiency 1
  • <45 ng/mL provides 85% sensitivity and 92% specificity for iron deficiency 1
  • Values 12-100 μg/dL may still indicate iron deficiency in patients with concurrent inflammation, malignancy, or liver disease 1

  • 100 μg/dL essentially excludes iron deficiency 1

Adjunctive Iron Studies

• Transferrin Saturation (TSAT): <30% supports iron deficiency diagnosis, particularly useful when ferritin is equivocal due to inflammation 1
• Reticulocyte Count: Low count suggests inadequate bone marrow response; helps distinguish iron deficiency from hemolysis 1

Important caveat: In patients with chronic inflammatory conditions or chronic kidney disease, ferritin may be falsely elevated as an acute-phase reactant. In these cases, use transferrin saturation, C-reactive protein, or soluble transferrin receptor to clarify iron status 1

Identifying the Underlying Cause

History and Physical Examination Focus

• Menstrual history: Heavy menstrual bleeding is the most common cause in premenopausal women 1
• Dietary assessment: Document vegetarian/vegan diet, but do not accept this as sole explanation without full GI evaluation 1
• Medication review: NSAIDs, aspirin, and anticoagulants increase GI bleeding risk 1
• Blood donation history: Frequent donation can cause iron deficiency 1
• Family history: Screen for hemoglobinopathies (thalassemia), hereditary hemorrhagic telangiectasia, and bleeding disorders 1

Gastrointestinal Evaluation for Men and Postmenopausal Women

All men and postmenopausal women with confirmed iron deficiency anemia require bidirectional endoscopy (both upper endoscopy and colonoscopy) to exclude GI malignancy, even without GI symptoms. 1

• Upper GI endoscopy with small bowel biopsies: Identifies 30-50% of causes and detects celiac disease in 2-3% of IDA patients 1

  • Small bowel biopsies are mandatory during upper endoscopy to screen for celiac disease 1
  • If endoscopy is not feasible, perform barium study plus antiendomysial antibody testing 1

• Colonoscopy or double-contrast barium enema: Essential even if upper endoscopy reveals a lesion, as dual pathology occurs in 10-15% of patients 1

  • Do not accept findings of esophagitis, erosions, or peptic ulcer as the sole cause without completing lower GI evaluation 1

• Further small bowel evaluation: Only pursue if anemia is transfusion-dependent or visible blood loss occurs 1

  • Consider enteroscopy for small bowel angiodysplasia in transfusion-dependent cases 1
  • Small bowel radiology rarely useful unless Crohn's disease suspected 1

Special Populations

• Premenopausal women: If heavy menstrual bleeding is documented and no other risk factors exist, GI evaluation may be deferred initially 1
• Chronic kidney disease patients: Use gender-specific ferritin thresholds (<25 ng/mL for males, <11 ng/mL for females) and investigate for GI bleeding if no other iron losses identified 1

Diagnostic Confirmation

A therapeutic trial of oral iron for 3 weeks with appropriate hemoglobin response (rise of 0.25-0.4 g/dL/day after reticulocytosis) confirms iron deficiency when laboratory tests are equivocal. 1, 2

Bone marrow aspiration is the gold standard but rarely necessary in clinical practice 1

Common Pitfalls to Avoid

• Do not skip GI evaluation in men or postmenopausal women based on dietary history alone—full investigation is mandatory 1
• Do not accept a single upper GI lesion as the cause without completing colonoscopy due to high dual pathology rate 1
• Do not rely on ferritin alone in inflammatory states—add transferrin saturation or C-reactive protein 1
• Do not assume thalassemia in ethnic populations without confirmatory hemoglobin electrophoresis 1