What is the appropriate management for a patient with leukocytosis, neutrophilia, and hypochromic anemia?

Management of Leukocytosis, Neutrophilia, and Hypochromic Anemia

Immediate Priority: Investigate the Underlying Cause of Iron Deficiency

The appropriate management is oral iron supplementation with ferrous sulfate 200 mg three times daily for at least three months after anemia correction, while simultaneously investigating the source of iron loss through gastrointestinal evaluation, given the patient's leukocytosis and neutrophilia are likely reactive to the severe iron deficiency. 1, 2

Diagnostic Confirmation

The laboratory findings confirm iron deficiency anemia:

• MCV 81 fL (low-normal), MCH 25.0 pg (reduced), and MCHC 310 g/L (reduced) with hypochromic red cells on film are characteristic of iron deficiency 1, 2
• The RDW of 14% with low MCV strongly suggests iron deficiency rather than thalassemia minor 1
• MCH is a more reliable marker than MCV for iron deficiency as it's less dependent on storage conditions 1

Understanding the Leukocytosis

The elevated white cell count (15.4 × 10⁹/L) with neutrophilia (8.9 × 10⁹/L) and lymphocytosis (5.7 × 10⁹/L) requires context:

• Severe iron deficiency anemia can cause reactive thrombocytosis and leukocytosis, which typically resolve with iron supplementation 3
• Leukocytosis in the setting of iron deficiency is exceptional but well-documented, and should normalize as the anemia corrects 3
• The peripheral smear showing rouleaux formation without blasts or toxic granulations makes acute infection or hematologic malignancy less likely 4, 5

However, infection must still be excluded:

• Leukocytosis is a common sign of infection, particularly bacterial, and requires identification of other signs and symptoms 4
• Assess for fever, localizing symptoms, or signs of systemic infection before attributing leukocytosis solely to iron deficiency 4

Iron Replacement Protocol

First-line treatment:

• Ferrous sulfate 200 mg three times daily is the standard treatment 6, 1, 2
• Alternative formulations (ferrous gluconate or ferrous fumarate) can be used if ferrous sulfate is not tolerated 6, 1, 2
• Adding ascorbic acid enhances iron absorption and should be considered if response is poor 6, 1

Expected response:

• Hemoglobin should rise ≥10 g/L (or ≥2 g/dL) within 2-4 weeks, confirming iron deficiency 1, 2
• Continue iron supplementation for three months after anemia correction to replenish iron stores 6, 1, 2

If no response occurs:

• Consider non-compliance, ongoing blood loss, malabsorption, or rare genetic disorders 1
• Intravenous iron should be considered if malabsorption is present 1, 2

Mandatory Investigation for Source of Iron Loss

This is critical and cannot be deferred:

• All adults with confirmed iron deficiency anemia warrant investigation for the source of iron loss 1, 2
• Men with Hb <110 g/L or non-menstruating women with Hb <100 g/L should receive fast-track gastrointestinal referral 1, 2
• Investigation should be considered at any level of anemia with confirmed iron deficiency, especially with more severe degrees 1

Specific investigations needed:

• Evaluate for gastrointestinal blood loss through history of melena, hematochezia, or occult bleeding 1
• Consider upper endoscopy and colonoscopy to exclude malignancy or other bleeding sources 6, 2
• Screen for celiac disease if malabsorption is suspected 1
• In premenopausal women, assess for menorrhagia as the most common cause 6, 1

Monitoring Strategy

Short-term monitoring:

• Recheck complete blood count in 2-4 weeks to confirm hemoglobin rise and resolution of leukocytosis 1, 2, 3
• The leukocytosis and neutrophilia should normalize as the anemia improves if they are reactive 3

Long-term monitoring:

• Monitor hemoglobin concentration and red cell indices at three-monthly intervals for one year, then after a further year 6, 1, 2
• Check serum ferritin and transferrin saturation to assess iron store repletion 2
• Provide additional oral iron if hemoglobin or MCV falls below normal 6, 1

Critical Pitfalls to Avoid

• Do not assume all leukocytosis is reactive without excluding infection—assess for fever, symptoms, and signs of bacterial infection 4
• Do not attribute the anemia solely to dietary deficiency without investigating for gastrointestinal blood loss or malignancy 1, 2
• Do not overlook combined deficiencies—check B12 and folate if response to iron is suboptimal 1
• If leukocytosis persists after anemia correction, consider referral to hematology to exclude primary hematologic disorder 4, 5
• Do not use hemoglobin electrophoresis routinely, but order it if microcytosis persists with normal iron studies or if MCV is disproportionately low 1