What could be causing anemia, low neutrophil count, and low ferritin and transferrin levels in a 15-year-old boy with a recent history of normal hemoglobin and hematocrit?

Differential Diagnosis: Anemia with Neutropenia and Low Iron Stores in an Adolescent

Most Likely Diagnosis

This clinical presentation most strongly suggests chronic gastrointestinal blood loss, likely from an underlying inflammatory bowel disease (IBD), given the combination of progressive iron deficiency anemia, neutropenia (which can occur with chronic inflammation or nutritional deficiencies), and monocytosis (a marker of chronic inflammation). 1

Diagnostic Approach

Iron Status Interpretation

The combination of low ferritin and low transferrin in the absence of documented inflammation indicates absolute iron deficiency from chronic blood loss. 1, 2

• Without inflammation present: Ferritin <30 μg/L confirms iron deficiency 1, 3
• With inflammation present: Ferritin up to 100 μg/L may still indicate iron deficiency 1, 3
• Low transferrin (rather than elevated) suggests either severe iron depletion or possible protein malnutrition 2, 4

Critical Differential Considerations

Primary causes to investigate urgently:

• Inflammatory bowel disease (Crohn's or ulcerative colitis): IBD affects 13-90% of patients with iron deficiency and commonly presents with anemia as the most frequent extraintestinal manifestation 1, 2
• Chronic gastrointestinal bleeding: From peptic ulcer disease, gastritis, or occult malignancy (though less likely at age 15) 2, 5
• Celiac disease: Causes malabsorption of iron and can present with neutropenia 2, 5
• Helicobacter pylori-associated atrophic gastritis: Impairs iron absorption 5

Secondary considerations for neutropenia:

• Vitamin B12 or folate deficiency: Can cause both anemia and neutropenia; must be evaluated given the neutropenia 6, 7
• Copper deficiency: Can occur with malabsorption and causes both anemia and neutropenia
• Bone marrow suppression: From chronic inflammation or nutritional deficiencies 7, 8

Essential Diagnostic Workup

Immediate laboratory testing needed:

• Inflammatory markers: CRP and ESR to assess for chronic inflammation 1, 3
• Complete nutritional assessment: Vitamin B12, folate, and reticulocyte count 1, 6, 7
• Transferrin saturation: Should be <20% in iron deficiency 1, 3, 2
• Soluble transferrin receptor (sTfR): If available, helps differentiate iron deficiency from anemia of inflammation (elevated in iron deficiency, normal in inflammation) 1, 4
• Mean corpuscular volume (MCV) and red cell distribution width (RDW): To characterize the anemia 1, 3

Critical clinical investigations:

• Upper and lower endoscopy: Essential to identify IBD or other GI pathology given the chronic blood loss pattern 1
• Celiac serologies: Tissue transglutaminase antibodies 2, 5
• Stool studies: Fecal calprotectin (elevated in IBD), occult blood testing 1
• H. pylori testing: Urea breath test or stool antigen 5

Management Strategy

Immediate Treatment

Iron supplementation is mandatory but route depends on underlying diagnosis:

• If no inflammation identified: Oral ferrous sulfate 325 mg daily or alternate days as first-line 1, 2
• If IBD or chronic inflammation confirmed: Intravenous iron is preferred over oral, as hepcidin-mediated blockade makes oral iron ineffective 3, 2, 7, 8
• Avoid oral iron if transferrin saturation <20% with ferritin >100 μg/L: This pattern suggests anemia of inflammation where oral iron will not be absorbed 3, 8

Addressing Underlying Cause

Treatment must target the primary disease process:

• For IBD: Control inflammation with appropriate IBD therapy; iron supplementation alone will fail without disease control 1, 3
• For celiac disease: Gluten-free diet is essential for iron absorption 2, 5
• For H. pylori: Eradication therapy improves iron absorption 5

Monitoring Neutropenia

The neutropenia requires specific attention:

• If vitamin B12 deficiency confirmed: Requires lifelong monthly B12 injections if pernicious anemia; oral supplementation if dietary deficiency 6
• Critical warning: Folic acid supplementation without B12 can mask B12 deficiency while allowing irreversible neurologic damage to progress 6
• Recheck complete blood count: 8-10 weeks after treatment initiation to assess response 3

Common Pitfalls to Avoid

• Do not assume low ferritin alone is sufficient: In a 15-year-old with 6 months of progressive anemia, the underlying cause must be identified 1
• Do not give folic acid empirically: This can mask B12 deficiency and allow neurologic complications 6
• Do not use oral iron if inflammation is present: Hepcidin elevation blocks absorption, making oral iron ineffective 3, 7, 8
• Do not ignore the neutropenia: This suggests either nutritional deficiency (B12, folate, copper) or bone marrow involvement requiring investigation 1, 6
• Do not delay endoscopy: Six months of progressive anemia in an adolescent warrants urgent GI evaluation 1

Geographic Consideration

Given the patient's residence in Mexico for 6 years, consider endemic parasitic infections (hookworm, whipworm) as additional causes of chronic GI blood loss and iron deficiency, though these typically don't cause neutropenia. 2