With a red blood cell count of 6.77 ×10⁶/µL, hemoglobin 16.2 g/dL, mean corpuscular volume 78 fL, mean corpuscular hemoglobin 23.8 pg, mean corpuscular hemoglobin concentration 30.4 g/dL, and red cell distribution width 19.6%, what is the most likely diagnosis and what investigations or management should be pursued?

Microcytic Anemia with Elevated RBC Count and Markedly Elevated RDW

The most likely diagnosis is iron deficiency anemia with compensatory erythrocytosis, though thalassemia trait must be definitively excluded given the elevated RBC count of 6.77 ×10⁶/µL. 1, 2

Laboratory Pattern Analysis

Your results show a classic microcytic hypochromic pattern:

• MCV 78 fL (microcytic) with MCH 23.8 pg and MCHC 30.4 g/dL (both low) indicate hypochromic red cells with decreased hemoglobin content per cell 1
• RBC count 6.77 ×10⁶/µL is markedly elevated, representing compensatory bone marrow response to reduced oxygen-carrying capacity per cell 2
• RDW 19.6% is significantly elevated, indicating marked variation in red cell size (anisocytosis) 1

The markedly elevated RDW (19.6%) is the critical discriminating feature that strongly favors iron deficiency over thalassemia trait. 1, 3

Differential Diagnosis

Iron Deficiency Anemia (Most Likely)

• Microcytosis with elevated RBC count occurs because the bone marrow increases erythropoietic activity to compensate for reduced hemoglobin per cell 2
• High RDW reflects the heterogeneous population of red cells produced during progressive iron depletion—older normocytic cells mixed with newer microcytic hypochromic cells 1
• Low MCHC specifically indicates severe iron-restricted erythropoiesis 4, 2

Thalassemia Trait (Must Be Excluded)

• Thalassemia trait also produces microcytosis with elevated RBC count (often >5.5 ×10⁶/µL) 1
• However, thalassemia typically shows RDW <14% because all red cells are uniformly small 1, 3
• The RDW/RBC ratio has 100% specificity for distinguishing thalassemia from iron deficiency, with values >3.0 indicating iron deficiency 3
• Your RDW/RBC = 19.6/6.77 = 2.89, which is borderline but the absolute RDW elevation makes iron deficiency more likely 3

Immediate Diagnostic Workup

Order the following tests within 24-48 hours: 1, 2

Essential Iron Studies

• Serum ferritin (most specific test): <15 μg/L confirms iron deficiency; <30 μg/L indicates depleted stores 1, 2
• Transferrin saturation: <16-20% supports iron deficiency 1, 2
• C-reactive protein (CRP): to identify inflammation that may falsely elevate ferritin 1, 2

Thalassemia Screening

• Hemoglobin electrophoresis or HPLC: to detect elevated HbA2 (>3.5%) diagnostic of beta-thalassemia trait 1, 5
• Parental MCV testing: if available, MCV <80 fL in both parents suggests hereditary hemoglobinopathy 1

Interpretation Algorithm

If Ferritin <30 μg/L (or <100 μg/L with inflammation):

Iron deficiency is confirmed. 1, 2

Immediately investigate the source of iron loss: 1

• Gastrointestinal evaluation: Upper endoscopy and colonoscopy for occult bleeding, especially if age >50 or alarm symptoms present 1
• Menstrual history: Heavy menstrual bleeding is the most common cause in premenopausal women 1
• Dietary assessment: Though inadequate intake alone rarely causes severe deficiency, document iron-poor diet 1
• Celiac serology: Tissue transglutaminase antibodies, as malabsorption is a common cause 1
• Stool guaiac testing: Screen for gastrointestinal blood loss 1

If Ferritin Normal and Hemoglobin Electrophoresis Shows Elevated HbA2:

Beta-thalassemia trait is confirmed. 1, 5

• No iron supplementation needed 1
• Genetic counseling if planning pregnancy 1
• Monitor for concurrent iron deficiency (can coexist) 1

If Both Iron Studies and Hemoglobin Electrophoresis Are Normal:

Consider combined deficiency or anemia of chronic disease. 1, 2

• Check vitamin B12 and folate (combined deficiency can normalize MCV) 1, 2
• Evaluate for chronic inflammatory conditions 1, 2

Treatment for Confirmed Iron Deficiency

Initiate oral iron supplementation immediately while investigating the underlying cause: 2

• Ferrous sulfate 325 mg (65 mg elemental iron) once to three times daily between meals 2
• Expect hemoglobin increase of 1-2 g/dL every 2-4 weeks 2
• Continue for 3-6 months after hemoglobin normalizes to replenish iron stores 2
• Recheck CBC and iron studies at 4-8 weeks to confirm response 2

Consider intravenous iron if: 2

• Intolerance to oral iron (nausea, constipation)
• Malabsorption (celiac disease, inflammatory bowel disease)
• Ongoing blood loss exceeding oral replacement capacity
• Severe anemia requiring rapid correction

Critical Pitfalls to Avoid

• Do not assume thalassemia based solely on elevated RBC count—the high RDW strongly argues against it 1, 3
• Do not dismiss normal ferritin in the presence of inflammation—use higher cutoffs (up to 100 μg/L) 1, 2
• Do not start iron supplementation without investigating the underlying cause—gastrointestinal malignancy must be excluded 1
• Do not rely on MCV alone—MCH and MCHC are more sensitive early markers of iron deficiency 2, 6
• Do not forget that iron deficiency and thalassemia can coexist—if hemoglobin electrophoresis shows thalassemia trait but ferritin is low, treat both conditions 1

Special Consideration: Cyanotic Heart Disease

If this patient has cyanotic congenital heart disease, iron deficiency superimposed on compensatory polycythemia creates a particularly dangerous situation: 1, 4

• Iron-deficient microcytic cells are rigid and less deformable, increasing risk of cerebrovascular accidents 1
• Microcytosis from iron deficiency was the strongest independent predictor of stroke in cyanotic patients 1
• Never perform phlebotomy in these patients—it worsens iron deficiency 1
• Aggressive iron repletion is essential 1, 4