Given a CBC with RBC count 6.14 million/µL, hemoglobin 11.6 g/dL, hematocrit 41.4 %, MCV 67.4 fL, MCH 18.9 pg, MCHC 28.0 g/dL, and RDW 15.8 %, what is the most likely cause of anemia and what diagnostic and treatment steps are recommended?

Microcytic Hypochromic Anemia with Elevated RBC Count: Iron Deficiency Anemia

This CBC pattern—microcytic (MCV 67.4 fL), hypochromic (MCH 18.9 pg, MCHC 28.0 g/dL) anemia with an elevated RBC count (6.14 million/µL) and elevated RDW (15.8%)—is most consistent with iron deficiency anemia, and you should immediately order serum ferritin, iron studies (serum iron, TIBC, transferrin saturation), and a peripheral blood smear to confirm the diagnosis.

Understanding the CBC Pattern

The combination of findings here is highly characteristic:

• Microcytosis (MCV 67.4 fL): Severe microcytosis below 80 fL most commonly indicates iron deficiency, though thalassemia and anemia of chronic disease are differential considerations 1
• Hypochromia: Both MCH (18.9 pg) and MCHC (28.0 g/dL) are markedly reduced, indicating insufficient hemoglobin in red cells—a hallmark of iron deficiency 2
• Elevated RBC count (6.14 million/µL): This paradoxical finding occurs because the bone marrow compensates for low hemoglobin by producing more red cells, though each cell is smaller and paler 3
• Elevated RDW (15.8%): Increased red cell size variability reflects the mixed population of older normal-sized cells and newer microcytic cells, strongly supporting iron deficiency over thalassemia trait (which typically has normal RDW) 4, 5

Diagnostic Algorithm

Immediate Next Steps

1. Serum ferritin (most powerful test for iron deficiency):

   • <15 µg/L: Diagnostic of iron deficiency 6
   • <30 µg/L: Indicates low iron stores 2
   • <45 µg/L: Consider iron deficiency, especially with inflammation 2

   • 100 µg/L: Iron deficiency almost certainly not present 6

2. Iron studies:

   • Transferrin saturation <15% confirms absolute iron deficiency 1
   • Low serum iron with elevated TIBC supports diagnosis 1

3. Peripheral blood smear: Essential to confirm microcytosis, hypochromia, and rule out other causes 1

Distinguishing Iron Deficiency from Thalassemia Trait

The elevated RBC count raises the possibility of thalassemia trait, but several features favor iron deficiency:

• Elevated RDW: Thalassemia trait typically has normal or only slightly elevated RDW, while iron deficiency shows marked elevation 4, 5
• Severity of microcytosis: While both cause microcytosis, the pattern differs
• If ferritin is low: This confirms iron deficiency 6
• If ferritin is normal with appropriate ethnic background: Order hemoglobin electrophoresis to exclude thalassemia 2, 6

Investigation for Underlying Cause

Once iron deficiency is confirmed, investigate the source of blood loss or malabsorption:

History Focus

• Gastrointestinal symptoms: Any abdominal pain, change in bowel habits, blood in stool 6
• Menstrual history: If premenopausal woman, quantify menstrual blood loss 6
• Medications: NSAIDs, aspirin, anticoagulants 6
• Dietary intake: Assess iron-rich food consumption, vegetarian/vegan diet 6
• Family history: Bleeding disorders, GI malignancy, celiac disease 6

Gastrointestinal Investigation

For adults (especially >45 years or with concerning symptoms):

1. Upper endoscopy with small bowel biopsies:

   • Identifies gastric cancer, peptic ulcer disease, angiodysplasia
   • Small bowel biopsies detect celiac disease (present in 2-3% of IDA cases) 6
   • Expected to reveal cause in 30-50% of patients 6

2. Colonoscopy or barium enema:

   • Essential even if upper endoscopy finds a lesion (dual pathology occurs in ~10% of cases) 6
   • Excludes colorectal cancer, polyps, inflammatory bowel disease 6

3. Anti-endomysial antibody testing: If endoscopy not immediately available or patient <45 years without alarm symptoms 6

Common pitfall: Do not assume dietary deficiency or menstruation is the sole cause without excluding GI pathology, as asymptomatic malignancies frequently present with IDA 6

Treatment Approach

Iron Supplementation

Start immediately while investigating underlying cause:

• Ferrous sulfate 200 mg three times daily (most cost-effective) 6
• Alternatives if not tolerated: ferrous gluconate or ferrous fumarate 6
• Co-administer with vitamin C to enhance absorption 6
• Avoid tea and coffee around dosing times (impair absorption) 7

Monitoring Response

• Hemoglobin should rise by 2 g/dL after 3-4 weeks 6
• Failure to respond indicates:
  • Poor compliance (most common)
  • Continued blood loss
  • Malabsorption
  • Misdiagnosis 6

Parenteral Iron

Reserve for:

• Intolerance to at least two oral preparations
• Documented malabsorption (e.g., celiac disease)
• Not recommended routinely as response is no faster than oral therapy and carries risk of anaphylaxis 6

Key Clinical Caveats

• Do not delay investigation based on hemoglobin level: Even mild anemia with iron deficiency warrants evaluation, as severity does not predict presence of serious pathology 2, 6
• Ferritin can be falsely elevated: As an acute phase reactant, ferritin may appear normal in iron deficiency with concurrent inflammation, malignancy, or liver disease 2, 6
• Reticulocyte count: If available, a low reticulocyte index (<2.0) confirms decreased RBC production consistent with iron deficiency 1
• Resolution timeline: Aim for anemia resolution within 6 months; persistent anemia requires further investigation 6