What type of anemia is indicated by a hemoglobin of 10.4 g/dL, mean corpuscular volume of 92 fL, total iron‑binding capacity of 347 µg/dL, transferrin saturation of 16 %, and ferritin of 26 ng/mL?

Iron-Deficiency Anemia

This patient has iron-deficiency anemia. The combination of hemoglobin 10.4 g/dL (anemia), ferritin 26 ng/mL (depleted iron stores), transferrin saturation 16% (borderline iron deficiency), elevated TIBC 347 µg/dL (compensatory increase in iron-binding capacity), and normal MCV 92 fL (early iron deficiency before microcytosis develops) definitively establishes this diagnosis. 1

Diagnostic Interpretation

Iron Studies Confirm Absolute Iron Deficiency

• Ferritin 26 ng/mL is below the 30 µg/L threshold that confirms iron deficiency in the absence of inflammation. 1 This level indicates depleted iron stores with 100% specificity in women of childbearing age when ferritin falls below 15 µg/L, and your patient's value of 26 ng/mL is only marginally above this cutoff. 1

• Transferrin saturation of 16% meets the diagnostic threshold for iron deficiency in adults (TSAT < 16–20%). 2, 1 This indicates that only 16% of transferrin molecules are carrying iron, reflecting inadequate iron availability for hemoglobin synthesis.

• TIBC of 347 µg/dL is elevated (normal range approximately 250–370 µg/dL), which occurs when the body increases transferrin production to capture any available circulating iron in response to depleted stores. 1 A TIBC ≥ 350 µg/dL has 54% predictive value for iron deficiency. 3

Normal MCV Does Not Exclude Iron Deficiency

• The MCV of 92 fL is normal, but this does not rule out iron deficiency. In early iron deficiency, the MCV remains normal because older red cells with adequate hemoglobin content are still circulating alongside newer iron-deficient cells. 4 Microcytosis (MCV < 80 fL) develops only after prolonged iron depletion. 2

• Over 50% of patients with confirmed iron deficiency (low ferritin and low iron with elevated TIBC) have normal MCV values. 5 The MCV has only 43–48% sensitivity for detecting iron deficiency, meaning it misses more than half of cases. 5

• Relying on MCV alone to diagnose or exclude iron deficiency will miss the majority of early cases. 4 Ferritin and transferrin saturation are far more reliable diagnostic markers. 1

Mandatory Evaluation for Underlying Cause

Gastrointestinal Blood Loss

• Iron deficiency in adults mandates investigation for gastrointestinal pathology, including malignancy. 2, 1 Even mild anemia requires endoscopic evaluation in postmenopausal women and all men to exclude treatable sources of chronic blood loss. 1

• Perform stool guaiac testing immediately to screen for occult gastrointestinal bleeding. 1 If positive, proceed to upper endoscopy with duodenal biopsies and colonoscopy. 1

Menstrual Blood Loss

• If the patient is premenopausal, assess menstrual history for heavy bleeding (menorrhagia), which is a leading cause of iron deficiency in women. 2 Heavy menstrual bleeding is defined as soaking through a pad or tampon every 1–2 hours or periods lasting longer than 7 days.

Malabsorption Disorders

• Screen for celiac disease with tissue transglutaminase IgA antibodies and total IgA, as celiac disease accounts for 3–5% of iron-deficiency anemia cases. 1 Consider inflammatory bowel disease if the patient has diarrhea, abdominal pain, or weight loss. 1

Dietary Insufficiency

• Evaluate dietary iron intake, particularly in patients following vegetarian or vegan diets, as non-heme iron from plant sources is poorly absorbed compared to heme iron from meat. 2

Treatment Recommendations

First-Line Oral Iron Therapy

• Initiate ferrous sulfate 325 mg (65 mg elemental iron) once daily on an empty stomach (≥1 hour before or ≥2 hours after meals) to maximize absorption. 1 Alternatively, prescribe ferrous gluconate 325 mg (38 mg elemental iron) or ferrous fumarate 325 mg (106 mg elemental iron). 1

• Expect a hemoglobin rise of 1–2 g/dL within 4–8 weeks if the diagnosis is correct and the patient is adherent. 1 This response confirms iron-deficiency anemia. 6

• Consider alternate-day dosing (every other day) rather than daily dosing, as daily iron raises hepcidin for up to 24 hours and blocks subsequent absorption. 2, 1 Alternate-day dosing markedly improves fractional iron absorption. 1

Indications for Intravenous Iron

Switch to intravenous iron if any of the following apply:

• Gastrointestinal intolerance to oral iron (nausea, constipation, diarrhea, dyspepsia). 2, 1

• Lack of hematologic response after 4–8 weeks of adequate oral therapy (persistent anemia despite adherence). 2, 1

• Chronic kidney disease with eGFR < 30 mL/min/1.73 m², as uremia impairs iron absorption. 1

• Documented malabsorption (celiac disease, inflammatory bowel disease, post-bariatric surgery). 1

• Ongoing blood loss that exceeds the replacement capacity of oral iron. 1

Intravenous Iron Options

Formulation	Maximum Single Dose	Special Considerations
Ferric carboxymaltose	1,000 mg	Rapid administration; low hypersensitivity risk [1]
Ferric derisomaltose	1,000 mg or 20 mg/kg (max 1,500 mg)	FDA-approved for total-dose infusion [1]
Iron sucrose	200 mg	No test dose required [2]
Low-molecular-weight iron dextran	High-dose infusion	Requires test dose due to anaphylaxis risk [2]

Treatment Targets

• Ferritin ≥ 100 ng/mL to ensure sufficient iron stores. 1

• Transferrin saturation ≥ 20% to confirm adequate iron availability for erythropoiesis. 1

• Hemoglobin ≥ 12 g/dL in adult females and ≥ 13 g/dL in adult males to consider anemia corrected. 1

Monitoring and Follow-Up

• Repeat complete blood count and iron studies 4–8 weeks after starting oral iron or after the last intravenous iron infusion. 1 Do not measure iron parameters within 4 weeks of IV iron administration, as circulating iron will falsely elevate results. 1

• If hemoglobin does not rise after 4–8 weeks of oral iron, reassess adherence, evaluate for ongoing occult bleeding or malabsorption, repeat iron studies, and consider switching to intravenous iron or investigating alternative diagnoses (thalassemia trait, anemia of chronic disease). 6

Common Pitfalls to Avoid

• Do not dismiss iron deficiency based on a normal MCV. More than half of iron-deficient patients have normal MCV values in early disease. 5, 4

• Do not rely on serum iron or TIBC alone to diagnose iron deficiency. These tests have high day-to-day variability and are influenced by recent meals, diurnal changes, and inflammation. 1 Ferritin and transferrin saturation are far more reliable. 1

• Do not delay investigation of the underlying cause. Iron deficiency rarely occurs without an identifiable source of loss or inadequate intake. 1 Gastrointestinal evaluation is mandatory in men and postmenopausal women. 1

• Do not continue oral iron indefinitely without reassessment. Lack of response after 4–8 weeks warrants evaluation for malabsorption, ongoing loss, or transition to intravenous iron. 1

• Do not measure C-reactive protein only if ferritin is borderline. Inflammation can falsely elevate ferritin and mask iron deficiency even when ferritin appears "normal" (30–100 ng/mL). 1 In the presence of inflammation, ferritin up to 100 µg/L may still be consistent with iron deficiency. 2