What is the most likely diagnosis and appropriate management for a patient with hemoglobin 99 g/L, mean corpuscular volume 77 fL, mean corpuscular hemoglobin 22 pg, red‑cell distribution width 18.1 % and a normal fecal immunochemical test?

Microcytic Anemia with Elevated RDW: Iron Deficiency Anemia

This patient has iron-deficiency anemia (IDA) and requires immediate iron studies (serum ferritin and transferrin saturation) followed by gastrointestinal evaluation to identify the source of blood loss, even though the fecal immunochemical test is normal.

Diagnostic Interpretation

The combination of low hemoglobin (99 g/L), microcytosis (MCV 77 fL), low MCH (22 pg), and markedly elevated RDW (18.1%) is pathognomonic for iron-deficiency anemia. 1 This pattern reflects a bone marrow producing progressively smaller, more hypochromic red cells as iron stores become depleted, creating a heterogeneous population of both older normal-sized cells and newer microcytic cells. 2

• MCH is a more reliable marker of iron deficiency than MCV because it directly measures hemoglobin content per cell and is less dependent on laboratory equipment or storage conditions. 2, 3 Your patient's MCH of 22 pg is well below the normal range (27–32 pg).

• The elevated RDW (18.1%) is a critical diagnostic clue that distinguishes iron deficiency from thalassemia trait, which typically presents with microcytosis but a normal or only slightly elevated RDW (≤14%). 1, 2

• A normal fecal immunochemical test does NOT exclude gastrointestinal blood loss as the cause of iron deficiency, because occult bleeding can be intermittent and the test has imperfect sensitivity for slow, chronic blood loss. 4

Required Diagnostic Workup

First-Line Laboratory Tests

• Order serum ferritin immediately. A ferritin <30 µg/L confirms iron deficiency in the absence of inflammation; if inflammation is present (check C-reactive protein), ferritin up to 100 µg/L may still indicate iron deficiency. 1, 3

• Obtain transferrin saturation (TSAT). A TSAT <15–20% supports iron deficiency and is less influenced by inflammatory states than ferritin. 1, 2, 3

• Measure absolute reticulocyte count. A low or inappropriately normal reticulocyte count confirms inadequate bone marrow response to anemia, consistent with iron-deficiency anemia rather than hemolysis or acute blood loss. 1, 2

• Check C-reactive protein to interpret ferritin accurately, because ferritin is an acute-phase reactant that can be falsely elevated during inflammation, infection, or malignancy despite true iron deficiency. 1, 3

Gastrointestinal Evaluation

All adult men and postmenopausal women with confirmed iron-deficiency anemia require bidirectional endoscopy (upper endoscopy with duodenal biopsies and colonoscopy) to exclude gastrointestinal malignancy, even when the fecal immunochemical test is normal. 1, 2

• Upper endoscopy should include small bowel biopsies because 2–3% of patients with iron-deficiency anemia have celiac disease as the underlying cause. 1, 3

• Common gastrointestinal causes of occult blood loss include colon cancer, gastric cancer, angiodysplasia, NSAID-induced gastropathy, and inflammatory bowel disease. 1

• In premenopausal women, menstrual blood loss is the most common cause of iron deficiency, but gastrointestinal evaluation is still warranted if iron supplementation fails to correct the anemia or if there are any gastrointestinal symptoms. 1

Treatment Approach

• Initiate oral ferrous sulfate 325 mg (65 mg elemental iron) once to three times daily while awaiting confirmatory iron studies and endoscopic evaluation. 2, 5

• A rise in hemoglobin after 4–6 weeks of oral iron therapy confirms the diagnosis of iron-deficiency anemia when other tests are equivocal. 1, 2

• If hemoglobin does not improve after 4–6 weeks, reassess adherence, evaluate for ongoing occult bleeding or malabsorption (celiac disease, inflammatory bowel disease, prior gastric surgery), repeat iron studies, and consider alternative diagnoses such as thalassemia trait or anemia of chronic disease. 2, 3

Critical Pitfalls to Avoid

• Do not assume dietary insufficiency is the sole cause of iron deficiency in adults; gastrointestinal blood loss must be excluded even when dietary intake appears inadequate. 1

• Do not rely solely on fecal immunochemical testing to rule out gastrointestinal pathology, because the test has limited sensitivity for slow, intermittent bleeding and does not detect upper gastrointestinal lesions reliably. 4

• Do not interpret ferritin without measuring C-reactive protein, because inflammation can mask iron deficiency by falsely elevating ferritin levels. 1, 3

• Do not confuse iron-deficiency anemia with thalassemia trait. Thalassemia typically presents with marked microcytosis (MCV <75 fL), a normal or low-normal RDW (<14%), and normal iron studies; hemoglobin electrophoresis is indicated if iron studies are normal. 1, 2, 3

• Do not delay gastrointestinal evaluation while treating with iron supplementation, because early detection of gastrointestinal malignancy significantly impacts morbidity and mortality. 1