In a patient with a CBC showing normal white‑blood‑cell count, neutrophil predominance, low lymphocyte proportion, hemoglobin 12.3 g/dL, hematocrit 40.5 %, MCV 80 fL, low MCH and MCHC, and RDW at the upper limit of normal, what is the most likely cause of the anemia and what initial work‑up and treatment should be pursued?

Microcytic Iron Deficiency Anemia

This patient has microcytic anemia (MCV 80 fL at lower limit of normal) with low MCH (24.3 pg) and low MCHC (30.4 g/dL), which most commonly indicates iron deficiency anemia, and the initial work-up should include serum ferritin, transferrin saturation (TSAT), and a reticulocyte count to confirm the diagnosis and guide treatment. 1

Understanding the CBC Pattern

The laboratory findings reveal:

• Microcytic indices: MCV 80 fL (borderline low-normal), MCH 24.3 pg (low), MCHC 30.4 g/dL (low)
• RDW 15.2%: At upper limit of normal, suggesting increased red cell size variation
• Normal hemoglobin (12.3 g/dL) and hematocrit (40.5%) for a female patient
• Neutrophil predominance (74%) with relative lymphopenia (16%) - likely a stress response or early inflammation

The combination of low MCH and MCHC with borderline-low MCV and elevated RDW is characteristic of iron-restricted erythropoiesis, most commonly from iron deficiency 1. The RDW elevation reflects the mixture of older normocytic cells and newer microcytic cells being produced under iron-deficient conditions 2, 3.

Algorithmic Diagnostic Work-Up

Step 1: Confirm Iron Deficiency

Order the following tests immediately 1, 4:

• Serum ferritin: <30 ng/mL confirms absolute iron deficiency; <12 ng/mL is diagnostic 1, 5
• Transferrin saturation (TSAT): <15% indicates iron deficiency 1
• Total iron binding capacity (TIBC): Elevated in iron deficiency
• Reticulocyte count: Should be low or inappropriately normal for the degree of anemia, indicating inadequate bone marrow response 1

Critical caveat: If ferritin is 30-100 ng/mL with concurrent inflammation (elevated CRP), functional iron deficiency may still be present 1, 4. In this scenario, TSAT <30% supports the diagnosis 4.

Step 2: Identify the Source of Iron Loss

Once iron deficiency is confirmed, investigate the underlying cause 5, 6:

For premenopausal women:

• Assess menstrual blood loss history (heavy or prolonged periods)
• Dietary iron intake assessment
• Consider gastrointestinal evaluation if menstrual losses don't explain severity

For all patients, look for:

• Gastrointestinal blood loss: Stool guaiac test, assess for melena or hematochezia 1
• Malabsorption: Screen for celiac disease (tissue transglutaminase antibodies), H. pylori infection, history of gastric surgery 5, 6
• Dietary insufficiency: Vegetarian/vegan diet, pica, restrictive eating
• Chronic NSAID use: Can cause occult GI bleeding 5

Red flags requiring urgent GI evaluation (upper endoscopy and colonoscopy) 5:

• Postmenopausal women or adult men with iron deficiency
• Positive fecal occult blood test
• GI symptoms (dysphagia, abdominal pain, change in bowel habits)
• Family history of GI malignancy
• Age >50 years with new-onset iron deficiency

Step 3: Peripheral Blood Smear Review

Request manual review to confirm 1:

• Hypochromic, microcytic red cells
• Pencil cells (elliptocytes)
• Absence of target cells (would suggest thalassemia)
• No basophilic stippling (would suggest lead poisoning or sideroblastic anemia)

Treatment Algorithm

Initial Treatment: Oral Iron 6

Start with oral ferrous iron salts (most cost-effective):

• Ferrous sulfate 325 mg (65 mg elemental iron) daily to three times daily
• Ferrous fumarate or ferrous gluconate are alternatives if not tolerated
• Take on empty stomach 1 hour before meals for optimal absorption, or with meals if GI side effects occur 6
• Add vitamin C 500 mg with each dose to enhance absorption 6

Expected response:

• Reticulocyte count should rise within 7-10 days
• Hemoglobin should increase by 1-2 g/dL within 3-4 weeks
• Continue for 3-6 months after normalization to replete iron stores

When to Use Intravenous Iron 6

Consider IV iron if:

• Intolerance to oral iron (nausea, constipation, abdominal pain)
• Malabsorption (celiac disease, inflammatory bowel disease, gastric bypass)
• No response to 4-6 weeks of oral iron therapy
• Severe anemia requiring rapid correction
• Ongoing blood losses exceeding oral replacement capacity

IV iron formulations: Iron sucrose, ferric carboxymaltose, or low-molecular-weight iron dextran 6

Common Pitfalls to Avoid

1. Don't assume menstruation explains all iron deficiency in premenopausal women - if ferritin is very low (<15 ng/mL) or anemia is severe, investigate for GI pathology 5

2. Don't miss thalassemia trait - if MCV is disproportionately low relative to hemoglobin (MCV <75 fL with near-normal Hb), RBC count is elevated (>5.5 million), and iron studies are normal, order hemoglobin electrophoresis 1

3. Don't overlook combined deficiencies - normal MCV with anemia may indicate concurrent iron and B12/folate deficiency; elevated RDW is a clue 1, 3

4. Don't stop investigating if initial GI work-up is negative - in transfusion-dependent patients or those with visible blood loss, consider video capsule endoscopy or deep enteroscopy for small bowel sources 6

5. The neutrophilia and lymphopenia are likely reactive - in the absence of fever, left shift, or other cytopenias, this pattern suggests physiologic stress rather than primary hematologic disease 7