What causes elevated RDW in a teenager with abnormal neutrophil and lymphocyte counts?

Differential Diagnosis: Neutropenia with Relative Lymphocytosis and Elevated RDW in an Adolescent

This 15-year-old boy most likely has iron deficiency anemia causing the elevated RDW (15.5%), while the neutrophil/lymphocyte pattern represents either a benign ethnic neutropenia, chronic viral infection, or early autoimmune process that requires systematic evaluation.

Primary Concern: Elevated RDW Analysis

The RDW of 15.5% is definitively elevated (normal ≤14.0%) and indicates heterogeneous red blood cell populations, which strongly suggests iron deficiency anemia rather than thalassemia trait or chronic disease 1. Iron deficiency typically presents with RDW >14.0% due to the presence of both older normal-sized cells and newer microcytic cells being produced under iron-deficient conditions 1, 2.

Essential Initial Laboratory Workup for RDW Elevation

• Serum ferritin (<30 μg/L confirms iron deficiency; <100 μg/L if inflammation present) is the crucial first test 2
• Complete blood count with MCV to assess for microcytosis (low MCV + high RDW = iron deficiency; low MCV + low RDW = thalassemia) 1, 2
• Transferrin saturation (<30% supports iron deficiency) 2
• C-reactive protein (CRP) to identify inflammatory states that can elevate RDW independent of iron status 2, 3
• Reticulocyte count to assess bone marrow response 4

Critical pitfall: Do not assume thalassemia trait based on ethnicity alone—the elevated RDW makes iron deficiency far more likely than thalassemia, which typically presents with RDW ≤14.0% 1, 2.

Secondary Concern: Neutrophil/Lymphocyte Pattern

Neutrophils at 40% (likely neutropenia for age) with lymphocytes in low 50s represents relative lymphocytosis. In a 15-year-old, this pattern warrants evaluation for:

Infectious Causes

• Chronic viral infections (EBV, CMV, HIV) commonly cause this pattern and can independently elevate RDW through chronic inflammation 3
• Recent or resolving acute viral illness where lymphocyte predominance persists 1

Autoimmune/Inflammatory Conditions

• Early autoimmune disease (SLE, rheumatoid arthritis) can cause both neutropenia and elevated RDW through chronic inflammation and oxidative stress 1, 3
• Autoimmune conditions increase RDW through multiple mechanisms including oxidative stress, inflammation, and altered erythrocyte survival 1, 3

Benign Ethnic Neutropenia

• Common in individuals of African, Middle Eastern, or West Indian descent
• Chronic, stable, asymptomatic neutropenia without increased infection risk
• Does not explain the elevated RDW

Nutritional Deficiencies

• Combined deficiencies (iron plus folate or B12) can present with complex hematologic patterns 2
• Vitamin B12 or folate deficiency alone typically causes elevated RDW but with macrocytosis, not the pattern described 1

Recommended Diagnostic Algorithm

Step 1: Confirm Iron Status

• Measure serum ferritin, transferrin saturation, and CRP simultaneously 2
• If ferritin confirms iron deficiency, investigate the source (dietary inadequacy vs. occult blood loss) 2
• In adolescent males, consider gastrointestinal blood loss from inflammatory bowel disease, celiac disease, or H. pylori gastritis 2

Step 2: Evaluate White Cell Pattern

• Peripheral blood smear to assess cell morphology and rule out dysplastic changes 4
• Viral serologies (EBV, CMV, HIV) if clinically indicated 1
• Autoimmune screening (ANA, anti-dsDNA, rheumatoid factor) if other systemic symptoms present 1
• Vitamin B12 and folate levels to exclude combined deficiencies 2

Step 3: Consider Hemoglobin Electrophoresis

• Only if MCV is low AND RDW normalizes after iron repletion, suggesting possible concurrent thalassemia trait 1, 2
• Do not perform initially—the elevated RDW makes isolated thalassemia trait unlikely 1, 2

Treatment Approach

If Iron Deficiency Confirmed

• Initiate oral iron supplementation (ferrous sulfate 325 mg daily or equivalent elemental iron 65 mg daily) 2
• Investigate dietary intake and consider nutritional counseling for adolescent males with high growth demands 1
• Recheck CBC in 4-6 weeks to confirm reticulocyte response and declining RDW 2
• Do not ignore persistent neutropenia—if it persists after iron repletion, pursue autoimmune or infectious workup 1

If Iron Studies Normal

• Hematology consultation for unexplained elevated RDW with abnormal differential 4
• Consider bone marrow evaluation if cytopenias worsen or additional cell lines affected 4

Critical Clinical Pearls

The elevated RDW is the most objective abnormality here and demands explanation—it reflects underlying metabolic derangement involving impaired erythropoiesis, oxidative stress, inflammation, or nutritional deficiency 3. In a 15-year-old, iron deficiency from rapid growth and inadequate dietary intake is the most common cause 1.

Never empirically treat with iron without confirming deficiency, as this can cause iron overload if thalassemia trait is present, though the elevated RDW makes this scenario unlikely 2. The neutrophil/lymphocyte pattern may be coincidental (benign ethnic neutropenia) or related to an underlying inflammatory/infectious process that also contributes to RDW elevation 1, 3.

RDW elevation reflects profound deregulation of erythrocyte homeostasis and has been associated with increased morbidity and mortality across multiple disease states, making it a marker that should never be dismissed as clinically insignificant 3.