What is the diagnosis and treatment for a patient with iron deficiency anemia, indicated by low iron levels and elevated TIBC?

Iron Deficiency Anemia Diagnosis

Your patient has iron deficiency anemia based on a TIBC of 246 mg/dL (low-normal) and serum iron of 30 mcg/dL, yielding a transferrin saturation of approximately 12%, which is well below the diagnostic threshold of 16%. 1

Diagnostic Interpretation

• Transferrin saturation of 12% confirms absolute iron deficiency, as values below 16% indicate insufficient iron available for erythropoiesis 1
• The TIBC of 246 mg/dL is at the lower end of normal (typically 250-450 mg/dL), which can occur in early iron deficiency or when inflammation is beginning to affect iron parameters 1
• Serum ferritin should be measured immediately to assess iron stores: levels <15 mcg/L indicate absolute iron deficiency (specificity 0.99), while levels <30 mcg/L generally indicate depleted iron stores 1
• If inflammation is present (elevated CRP or ESR), ferritin thresholds must be adjusted upward to 100 mcg/L as the lower limit of normal 1

Required Additional Testing

• Measure serum ferritin to quantify iron stores 1, 2
• Check inflammatory markers (CRP, ESR) to interpret ferritin accurately, as ferritin is an acute phase reactant 1
• Complete blood count with indices: assess for microcytosis (low MCV) and hypochromia (low MCH), though MCH is more reliable than MCV for detecting iron deficiency 1
• Hemoglobin electrophoresis if microcytosis is present with normal iron studies to exclude thalassemia 1

Investigating the Underlying Cause

All adults with confirmed iron deficiency anemia require investigation for gastrointestinal blood loss, except premenopausal women with menorrhagia. 1, 3, 4

For Men and Postmenopausal Women:

• Bidirectional endoscopy (gastroscopy AND colonoscopy) is mandatory to exclude gastrointestinal malignancy, as colorectal cancer is the most common serious cause 1, 3, 4
• Perform stool guaiac testing for occult blood 1
• Serological testing for celiac disease (tissue transglutaminase IgA with total IgA) before endoscopy 4

For Premenopausal Women:

• If menorrhagia is present and anemia is not severe, GI investigation may be deferred initially 1
• GI investigation is still warranted if: age >40 years, family history of GI malignancy, GI symptoms present, or failure to respond to oral iron therapy 1, 4

If Initial Endoscopy is Negative:

• Small bowel investigation (capsule endoscopy, CT/MRI enterography) should be performed if red flags exist: involuntary weight loss, abdominal pain, elevated CRP, or severe/refractory anemia 4
• Consider repeat endoscopy if anemia persists or worsens despite iron therapy 5

Treatment Approach

First-Line: Oral Iron Supplementation

Initiate oral iron therapy with 100-200 mg of elemental iron daily (ferrous sulfate 324 mg tablets contain 65 mg elemental iron, so prescribe 2-3 tablets daily). 6, 4

• Lower the dose to 65-100 mg elemental iron daily if gastrointestinal side effects occur (nausea, constipation, abdominal discomfort) 4
• Treatment duration: 3-6 months is typically required to normalize hemoglobin AND replenish iron stores 4
• Take on an empty stomach for optimal absorption, though may take with food if not tolerated 7
• Discontinue NSAIDs if the patient is taking them, as they contribute to GI blood loss 5

Second-Line: Intravenous Iron

Intravenous iron is indicated when: 7, 4, 8

• Oral iron causes intolerable side effects despite dose reduction
• Oral iron is ineffective after 4-6 weeks of adequate therapy
• Ongoing blood loss exceeds intestinal iron absorption capacity (e.g., angiodysplasia)
• Malabsorption is present (celiac disease, inflammatory bowel disease, post-bariatric surgery, atrophic gastritis)
• Severe anemia requiring rapid correction

Available IV formulations include iron sucrose, iron gluconate, and low-molecular-weight iron dextran, which have superior safety profiles compared to older preparations 7, 8

Critical Pitfalls to Avoid

• Never assume menstruation is the cause without excluding GI pathology in women >40 years or those with severe anemia 1
• Do not rely on ferritin alone in patients with inflammation—a ferritin between 30-100 mcg/L with low transferrin saturation suggests combined iron deficiency and anemia of chronic disease 1
• Avoid stopping investigation after negative initial endoscopy if anemia is severe, progressive, or unresponsive to iron therapy 5, 4
• Do not transfuse blood unless absolutely necessary (severe symptomatic anemia), as oral or IV iron is safer and effective 1