In an 11‑year‑old boy with hemoglobin 13.7 g/dL, hematocrit 40.9 % and mean corpuscular volume (MCV) 79 fL, what is the appropriate management?

Management of Microcytic Anemia in an 11-Year-Old Boy

This 11-year-old boy has microcytic anemia (MCV 79 fL) with normal hemoglobin for age, requiring immediate iron studies to differentiate iron deficiency from thalassemia trait, followed by targeted treatment based on those results.

Understanding the Laboratory Pattern

Hemoglobin and Hematocrit Interpretation

• The hemoglobin of 13.7 g/dL and hematocrit of 40.9% fall within the normal range for an 11-year-old male, as pediatric reference ranges differ from adult cutoffs and gradually increase during childhood to adult levels 1, 2.
• Despite normal hemoglobin, the low MCV of 79 fL (normal 80-100 fL) indicates microcytic red blood cells, which most commonly signals either iron deficiency or thalassemia trait 1.

Significance of Microcytosis Without Anemia

• Microcytosis can precede the development of frank anemia in iron deficiency, representing early iron-deficient erythropoiesis where the bone marrow produces progressively smaller red blood cells with less hemoglobin content 3.
• The presence of microcytosis alone warrants investigation because untreated iron deficiency will progress to overt anemia and can impact growth, cognitive development, and school performance in children 1.

Immediate Diagnostic Workup

Essential First-Line Tests

Order a complete iron panel immediately, including:

• Serum ferritin: The single most powerful test for confirming iron deficiency, with levels <30 μg/L confirming iron deficiency in the absence of inflammation 4, 3, 5.
• Transferrin saturation: Values <15-20% support iron deficiency and are less affected by inflammation than ferritin 3, 5.
• C-reactive protein (CRP): Essential for interpreting ferritin, as ferritin rises as an acute-phase reactant during inflammation and may mask true iron deficiency 3, 5.
• Red blood cell distribution width (RDW): A high RDW (>14%) combined with low MCV indicates iron deficiency anemia, whereas a low or normal RDW with low MCV suggests thalassemia trait 1.

Interpreting Ferritin in Context

• In the absence of inflammation (normal CRP), ferritin <30 μg/L confirms iron deficiency 1, 3.
• In the presence of inflammation, ferritin up to 100 μg/L may still indicate iron deficiency, requiring the higher threshold for diagnosis 1, 3.
• Ferritin >100 μg/L with inflammation makes absolute iron deficiency unlikely 1.

Differential Diagnosis Algorithm

If Iron Studies Confirm Iron Deficiency

Initiate oral iron supplementation immediately with:

• Ferrous sulfate 100-200 mg/day in divided doses (typical pediatric dosing based on weight and severity) 1.
• Administer iron between meals with vitamin C to enhance absorption 4.
• Expect hemoglobin to increase by approximately 1-2 g/dL every 2-4 weeks 3.
• Continue supplementation for 3-6 months after hemoglobin normalizes to replenish iron stores 4, 3.

Investigate the underlying cause of iron deficiency:

• Assess dietary intake of iron-rich foods (heme iron from meat, fortified cereals) 1.
• Evaluate for gastrointestinal blood loss, though less common in children than adults 1.
• Screen for malabsorption conditions such as celiac disease, particularly if there is poor response to oral iron 1, 5.
• Consider excessive cow's milk intake, which can displace iron-rich foods and cause occult GI blood loss in young children 1.

If Iron Studies Are Normal (Thalassemia Trait Likely)

Obtain hemoglobin electrophoresis to confirm thalassemia trait, particularly in children of Mediterranean, African, Middle Eastern, or Southeast Asian descent 3, 5.

Key distinguishing features of thalassemia trait:

• Low MCV disproportionate to the degree of anemia (MCV often 60-75 fL) 3.
• Normal or only slightly elevated RDW (<14%), unlike iron deficiency which typically shows RDW >14% 1.
• Normal or elevated red blood cell count despite microcytosis 6.
• Normal serum ferritin and transferrin saturation 3, 5.

Management of confirmed thalassemia trait:

• Do not prescribe iron supplementation, as it provides no benefit and may cause harm 5.
• Provide genetic counseling, especially if family planning is relevant 5.
• Reassure that thalassemia trait does not cause anemia or require treatment 5.
• Monitor for other causes of anemia if hemoglobin falls below normal for age 5.

Common Pitfalls and How to Avoid Them

Do Not Rely on MCV Alone

• Iron deficiency can present with normal MCV in early stages, and mean corpuscular hemoglobin (MCH) may be more sensitive than MCV for detecting early iron deficiency 3.
• Always obtain complete iron studies rather than assuming thalassemia based solely on microcytosis with normal hemoglobin 1.

Do Not Miss Mixed Deficiencies

• Concurrent iron and vitamin B12 deficiency can neutralize the MCV (one lowers it, one raises it), yielding a normal MCV but elevated RDW 5.
• If RDW is elevated despite normal MCV, measure vitamin B12 and folate levels in addition to iron studies 5.

Do Not Dismiss Inflammation

• In patients with acute or chronic inflammatory conditions, ferritin may be falsely elevated, masking true iron deficiency 1, 3.
• Use the higher ferritin threshold of 45-100 μg/L when CRP is elevated 3, 5.
• Consider measuring soluble transferrin receptor or reticulocyte hemoglobin content in complex cases where inflammation confounds iron status interpretation 1.

Do Not Forget to Monitor Response

• Recheck complete blood count and iron studies after 4-8 weeks of iron therapy to confirm response 3.
• Lack of hemoglobin increase after 4 weeks of adequate oral iron suggests either non-compliance, ongoing blood loss, malabsorption, or an incorrect diagnosis 1, 3.
• A rise in hemoglobin of ≥1 g/dL within 2-4 weeks confirms iron deficiency even if initial iron studies were equivocal 3, 5.

Practical Management Algorithm

1. Order iron studies (ferritin, transferrin saturation, CRP) and RDW immediately 4, 3, 5.

2. If ferritin <30 μg/L (or <100 μg/L with elevated CRP) and RDW >14%:

   • Diagnose iron deficiency anemia
   • Start oral iron supplementation
   • Investigate dietary causes and potential blood loss
   • Recheck CBC and iron studies in 4-8 weeks

3. If ferritin normal, transferrin saturation normal, and RDW ≤14%:

   • Obtain hemoglobin electrophoresis
   • Likely thalassemia trait
   • Provide genetic counseling
   • Do not give iron

4. If initial workup is inconclusive:

   • Consider a therapeutic trial of oral iron for 4 weeks
   • A rise in hemoglobin ≥1 g/dL confirms iron deficiency 1, 5
   • Refer to pediatric hematology if no response or if other cytopenias are present