In an adult with hemoglobin 11 g/dL and serum iron 30 µg/dL, what is the likely diagnosis and what work‑up and treatment should be recommended?

Diagnosis and Management of Anemia with Hemoglobin 11 g/dL and Serum Iron 30 µg/dL

This patient has iron deficiency anemia that requires immediate investigation for gastrointestinal blood loss and prompt initiation of iron replacement therapy. 1, 2

Diagnostic Confirmation

Calculate transferrin saturation (TSAT) immediately by obtaining total iron-binding capacity (TIBC) and using the formula: (serum iron × 100) ÷ TIBC. 1, 3 A TSAT < 20% confirms iron deficiency even when ferritin values are equivocal. 1, 3

Measure serum ferritin and C-reactive protein (CRP) to differentiate true iron deficiency from anemia of chronic disease. 1, 3 The interpretation depends critically on whether inflammation is present:

Without Inflammation (Normal CRP/ESR)

• Ferritin < 30 µg/L confirms absolute iron deficiency 1, 3
• Ferritin < 15 µg/L has 99% specificity for iron deficiency 1, 3, 2
• Ferritin > 100 µg/L essentially rules out iron deficiency 3

With Inflammation (Elevated CRP/ESR)

• Ferritin 30–100 µg/L with TSAT < 20% indicates true iron deficiency coexisting with anemia of chronic disease 1, 3
• Ferritin > 100 µg/L with TSAT < 20% defines anemia of chronic disease with functional iron deficiency 1, 3
• The ferritin threshold must be raised to < 100 µg/L in inflammatory conditions because ferritin is an acute-phase reactant 1, 3

Order a complete blood count with red-cell indices (MCV, MCH, RDW) and reticulocyte count. 3, 2 Expect microcytosis (low MCV), hypochromia (low MCH), and elevated RDW (> 14%) in iron deficiency. 3, 4

Investigation for Blood Loss

In adult men and postmenopausal women, gastrointestinal bleeding is the presumptive source until proven otherwise; occult malignancy must be excluded. 1, 4, 2

Perform bidirectional endoscopy (upper endoscopy plus colonoscopy) promptly because colorectal and gastric carcinomas are the most common serious causes of iron deficiency anemia in this population. 1, 4 Nine percent of patients older than 65 years with iron deficiency anemia have gastrointestinal cancer. 4

Do not delay endoscopic evaluation even if hemoglobin is above fast-track referral thresholds; investigation is indicated at any anemia level when iron deficiency is present. 1, 3

In premenopausal women, heavy menstrual bleeding is the most common cause, but gastrointestinal pathology must still be investigated if menstrual history does not fully explain the severity of anemia. 1, 2

Obtain a detailed medication history focusing on nonsteroidal anti-inflammatory drugs (NSAIDs) and aspirin, which are common causes of occult gastrointestinal bleeding. 1, 2

Screen for celiac disease with tissue transglutaminase (tTG) antibody testing at presentation, as malabsorption is an important consideration in the UK and high-income countries. 1, 3 If tTG is positive, confirm with small-bowel biopsy; if negative and no other features suggest celiac disease, duodenal biopsies are not required. 1

Iron Replacement Therapy

Start oral elemental iron 100–200 mg daily (e.g., ferrous sulfate 325 mg daily or on alternate days) immediately while diagnostic work-up proceeds. 3, 2 Alternate-day dosing may improve tolerability without compromising efficacy. 2

Continue therapy for at least 3–6 months after hemoglobin normalization to fully replenish iron stores, aiming for ferritin > 50 µg/L. 3

Recheck hemoglobin at one month; expect a 1–2 g/dL rise if treatment is effective. 4 Failure to respond indicates malabsorption, non-compliance, ongoing blood loss, or an undiagnosed lesion. 5, 4

Switch to intravenous iron if oral iron is poorly tolerated, malabsorption is documented (celiac disease, post-bariatric surgery), or hemoglobin fails to improve despite adherence. 3, 2 Intravenous iron is also preferred for ongoing blood loss and during the second and third trimesters of pregnancy. 2

Additional Diagnostic Considerations

Measure vitamin B12 and folate levels to exclude concomitant deficiencies that can impair marrow response to iron therapy. 3, 5

Assess renal function with serum creatinine and estimated glomerular filtration rate (eGFR) because chronic kidney disease is a common contributor to anemia. 1, 3

If microcytosis persists after iron repletion—or if the patient belongs to an at-risk ethnic group—order hemoglobin electrophoresis to exclude β-thalassemia trait. 3

Critical Pitfalls to Avoid

Do not rely on ferritin alone when inflammation is present; always calculate TSAT because functional iron deficiency can exist with high ferritin but low TSAT. 1, 3

Do not attribute iron deficiency solely to menstrual blood loss in perimenopausal women; gastrointestinal pathology must still be investigated. 3

Do not discontinue iron supplementation once hemoglobin normalizes; iron stores must be restored (target ferritin > 50 µg/L) to prevent rapid recurrence. 3

Do not postpone endoscopic investigation while awaiting response to iron therapy; malignancy work-up should proceed in parallel. 3

Do not diagnose thalassemia trait without first correcting iron deficiency, as the two conditions can coexist and iron deficiency can mask electrophoretic findings. 3