What is the interpretation and recommended management for a CBC showing low mean corpuscular volume (77 fL), low mean corpuscular hemoglobin (24 pg), and low mean corpuscular hemoglobin concentration (31.3 g/dL)?

Microcytic Hypochromic Anemia: Iron Deficiency Until Proven Otherwise

This CBC pattern—MCV 77 fL, MCH 24.0 pg, and MCHC 31.3 g/dL—indicates microcytic hypochromic anemia, which is iron deficiency in the overwhelming majority of cases. 1, 2

Immediate Diagnostic Workup

Order comprehensive iron studies immediately: serum ferritin, transferrin saturation (TSAT), serum iron, and total iron-binding capacity (TIBC). 1, 3 These tests will confirm iron deficiency and guide treatment decisions.

Measure C-reactive protein (CRP) to interpret ferritin correctly, because ferritin rises as an acute-phase reactant during inflammation and can mask true iron deficiency. 1, 3

Obtain an absolute reticulocyte count to assess bone marrow response; a low or inappropriately normal count confirms inadequate erythropoiesis typical of iron deficiency. 1, 3

Interpretation of Iron Studies

Without Inflammation (Normal CRP)

• Ferritin < 30 µg/L confirms iron deficiency. 1, 3
• TSAT < 15–16% supports iron deficiency and is less affected by inflammation than ferritin. 1, 3

With Inflammation (Elevated CRP)

• Ferritin up to 100 µg/L may still represent iron deficiency when inflammation is present. 1, 3
• TSAT < 20% with ferritin > 100 µg/L suggests anemia of chronic disease, not pure iron deficiency. 1

Differential Diagnosis: Thalassemia Trait

If iron studies are normal, obtain hemoglobin electrophoresis to evaluate for thalassemia trait, especially in patients of Mediterranean, African, Middle Eastern, or Southeast Asian ancestry. 3, 4

Thalassemia trait produces microcytic anemia but typically shows:

• Normal or elevated red blood cell count (often > 5.0 × 10¹²/L) 4
• Normal or low RDW (< 14%), whereas iron deficiency usually elevates RDW 1, 2
• MCV ≤ 73.8 fL and MCH ≤ 21.9 pg favor beta-thalassemia trait over HbE trait with > 90% sensitivity 4

Critical pitfall: Do not give iron supplementation to patients with thalassemia trait; instead, offer genetic counseling if planning pregnancy. 3

Investigation for Blood Loss

Once iron deficiency is confirmed, immediately perform stool guaiac testing to screen for gastrointestinal bleeding. 1, 3

All adult men and postmenopausal women with confirmed iron deficiency require endoscopic evaluation to exclude gastrointestinal malignancy, regardless of anemia severity. 3

In premenopausal women, assess menstrual history for heavy or prolonged bleeding as the likely source. 3

Evaluate for malabsorption conditions (celiac disease, inflammatory bowel disease, prior gastric surgery) that impair iron absorption. 3

Treatment Algorithm

Oral Iron Therapy (First-Line)

Start ferrous sulfate 325 mg once daily (or up to three times daily if tolerated) for confirmed iron deficiency. 3

Recent evidence supports intermittent dosing (every other day) as equally effective with fewer side effects than daily or twice-daily regimens. 5

Monitor hemoglobin response at 4–6 weeks; an increase confirms the diagnosis of iron-deficiency anemia and adequate absorption. 3

Intravenous Iron (Second-Line)

Reserve IV iron for patients who:

• Cannot tolerate oral iron due to gastrointestinal side effects 5
• Cannot absorb oral iron (malabsorption syndromes, inflammatory bowel disease) 5
• Do not respond to oral iron after 4–6 weeks 5
• Require rapid repletion (e.g., preoperative optimization) 3

Contemporary IV iron formulations (e.g., iron sucrose, ferric carboxymaltose) have rare allergic reactions, making them safe alternatives. 6, 5

Common Pitfalls to Avoid

Do not assume anemia of chronic disease without measuring iron studies, even in patients with known inflammatory conditions; up to 25–37.5% of patients with chronic kidney disease have concurrent iron deficiency. 1

Do not rely solely on hemoglobin or MCV to diagnose iron deficiency; more than 50% of women with documented iron deficiency are neither anemic nor microcytic at diagnosis. 7

Do not give empiric iron therapy without confirming the diagnosis, especially in elderly patients where microcytosis may indicate thalassemia trait, sideroblastic anemia, or early myelodysplastic syndrome. 1, 3

Do not overlook combined deficiencies; simultaneous iron and vitamin B12/folate deficiency can neutralize the MCV, yielding a normal MCV but elevated RDW. 1, 3

Special Populations

In chronic kidney disease (CKD) patients with serum creatinine ≥ 2 mg/dL, normocytic anemia is more common, but microcytic anemia still warrants iron studies because 25–37.5% have concurrent iron deficiency. 1

In cyanotic congenital heart disease patients, low MCHC indicates iron deficiency superimposed on polycythemia, creating rigid, less deformable red cells that increase microvascular complications. 2

Monitoring and Follow-Up

Repeat CBC and iron studies 4–6 weeks after initiating treatment to confirm response. 3

Continue iron supplementation for 3–6 months after hemoglobin normalizes to replenish iron stores. 3

If hemoglobin fails to rise after 4–6 weeks of adequate oral iron, reassess for:

• Ongoing blood loss 3
• Malabsorption 3
• Incorrect diagnosis (thalassemia trait, anemia of chronic disease) 1, 3
• Need for IV iron 5