What is the appropriate diagnosis and management for a patient with leukocytosis and anemia, as indicated by abnormal Complete Blood Count (CBC) and differential CBC results?

Diagnosis and Management of Leukocytosis with Anemia

This patient presents with neutrophilic leukocytosis (WBC 13.8 K/mcL with 88% neutrophils) and mild normocytic anemia (Hb 11.4 g/dL, Hct 34.5%), which most likely represents an acute inflammatory or infectious process requiring immediate investigation for the underlying cause, with iron studies and reticulocyte count as the next essential diagnostic steps. 1, 2

Interpretation of the CBC Findings

Leukocytosis Pattern

• The WBC of 13.8 K/mcL with marked neutrophilia (88%, absolute neutrophil count 12.14 K/mcL) and relative lymphopenia (7%) indicates an acute bacterial infection, inflammatory process, or physiologic stress response. 3, 4
• The absence of left shift (no bands reported) and normal platelet count (388 K/mcL) argues against severe sepsis or bone marrow pathology. 4, 5
• This degree of leukocytosis (WBC <15 K/mcL) is typically benign and reactive rather than representing primary bone marrow disease. 4, 5

Anemia Characteristics

• The hemoglobin of 11.4 g/dL meets WHO criteria for anemia in men (<13 g/dL) and non-pregnant women (<12 g/dL). 1, 6
• The normal MCV (85.8 fL) with low MCH (28.4 pcg) and normal MCHC (33.0 g/dL) suggests early iron deficiency or mixed anemia. 1, 2
• The elevated RDW (13.8%) indicates increased red cell size variation, which combined with low MCH strongly suggests iron-deficient erythropoiesis even before frank microcytosis develops. 1, 6

Immediate Diagnostic Workup

Essential Laboratory Tests

• Obtain iron studies immediately: serum ferritin, transferrin saturation (TSAT), and total iron-binding capacity to confirm or exclude iron deficiency. 1, 2, 6
  • Ferritin <30 μg/L confirms iron deficiency in the absence of inflammation. 1, 2, 6
  • TSAT <20% indicates functional or absolute iron deficiency. 1, 6
• Measure reticulocyte count to assess bone marrow response—low/normal suggests production defect while elevated suggests hemolysis or blood loss. 1, 6
• Check C-reactive protein (CRP) to assess for inflammation, as this affects ferritin interpretation. 3, 2, 6

Infection and Inflammation Workup

• Rule out infectious causes that commonly present with leukocytosis and anemia: obtain blood cultures, urinalysis with culture, and chest imaging if respiratory symptoms present. 3
• Consider stool studies including Clostridium difficile toxin if gastrointestinal symptoms are present. 3
• Measure ESR in addition to CRP to assess inflammatory burden. 3

Differential Diagnosis Priority

Most Likely Diagnoses

1. Acute infection (bacterial) with concurrent iron deficiency anemia or anemia of inflammation 3, 4, 7
2. Inflammatory condition (e.g., inflammatory bowel disease, rheumatologic disease) with secondary anemia 3
3. Combined iron deficiency and anemia of chronic disease 2, 6, 7

Red Flags Requiring Urgent Hematology Referral

• WBC >100 K/mcL would represent a medical emergency due to hyperviscosity risk, but this patient's WBC is only mildly elevated. 4
• Presence of blasts, immature cells, or concurrent severe thrombocytopenia/thrombocytosis would suggest primary bone marrow disorder. 4, 5
• Weight loss, bruising, hepatosplenomegaly, or lymphadenopathy would increase suspicion for hematologic malignancy. 3, 5

Management Algorithm

Step 1: Address Acute Process

• Identify and treat the underlying infection or inflammatory condition driving the leukocytosis—this is the priority as leukocytosis typically resolves with treatment of the underlying cause. 3, 4, 5
• The neutrophilic pattern strongly suggests bacterial infection requiring appropriate antibiotic therapy once cultures are obtained. 3, 4

Step 2: Anemia Management Based on Iron Studies

If Iron Deficiency Confirmed (Ferritin <30 μg/L, TSAT <20%):

• Initiate oral ferrous sulfate 200 mg three times daily for at least 3 months after anemia correction to replenish iron stores. 2, 8
• Adding ascorbic acid enhances absorption. 2
• In adult men and postmenopausal women, gastrointestinal evaluation with upper endoscopy and colonoscopy is mandatory to exclude GI malignancy as the source of blood loss. 2, 6
• Repeat CBC after 4-8 weeks; expect hemoglobin rise ≥10 g/L within 2 weeks if responding appropriately. 2

If Anemia of Inflammation (Ferritin >100 μg/L, TSAT <20%, elevated CRP):

• Treat the underlying inflammatory condition as the primary intervention—anemia typically improves with disease control. 1, 7
• Consider erythropoietin therapy only in specific situations such as chronic kidney disease. 1

If Mixed Picture (Ferritin 30-100 μg/L with inflammation):

• Soluble transferrin receptor levels may help distinguish iron deficiency from anemia of chronic disease. 6
• A trial of iron supplementation is reasonable while treating the underlying condition. 1, 2

Critical Pitfalls to Avoid

• Do not assume leukocytosis is benign without identifying the underlying cause—infection must be ruled out. 3, 4, 5
• Do not overlook iron deficiency because the MCV is still normal—the low MCH with elevated RDW indicates early iron deficiency. 1, 6
• Do not interpret ferritin without considering inflammatory status—ferritin can be falsely elevated in inflammation, masking true iron deficiency. 2, 6
• Do not start iron supplementation in adult men or postmenopausal women without investigating for GI blood loss. 2, 6
• Do not delay antibiotic therapy if bacterial infection is suspected while awaiting culture results. 3

Follow-up Monitoring

• Repeat CBC with differential in 1-2 weeks to ensure leukocytosis is resolving with treatment of underlying condition. 3, 5
• Monitor hemoglobin at 4-8 weeks after initiating iron therapy, then at 3-month intervals for one year. 2
• If leukocytosis persists without identified cause or worsens, refer to hematology for bone marrow evaluation. 4, 5