What is the appropriate diagnostic and treatment approach for a patient presenting with leukocytosis, microcytic hypochromic anemia, anisocytosis, and hyperimmunoglobulinemia?

Diagnostic Approach to Elevated WBC, Low MCV, Low MCH, Elevated RDW, and High IG

This presentation suggests two concurrent processes: microcytic hypochromic anemia (most likely iron deficiency) and leukocytosis with elevated immature granulocytes (IG), requiring immediate evaluation to exclude infection, malignancy, or acute inflammatory conditions.

Immediate Priority: Evaluate the Leukocytosis and Elevated IG

• Elevated immature granulocytes indicate left shift and suggest acute infection, severe inflammation, or hematologic malignancy 1
• Obtain a peripheral blood smear immediately to assess white blood cell morphology, maturity, and uniformity 1
• Look for specific clinical signs: fever, weight loss, bruising, fatigue, night sweats, or lymphadenopathy that would suggest hematologic malignancy 1
• Identify infection sources through history and examination: respiratory symptoms, urinary symptoms, skin infections, or recent trauma/surgery 1
• The peripheral white blood cell count can double within hours due to physiologic stressors including surgery, exercise, trauma, or emotional stress 1

If malignancy cannot be excluded or symptoms suggest hematologic disease (fever, weight loss, bruising, fatigue), immediate referral to hematology/oncology is indicated 1

Concurrent Evaluation: Microcytic Hypochromic Anemia

Initial Laboratory Testing

• Serum ferritin is the single most useful marker for iron deficiency, with a cutoff of 45 μg/L providing optimal sensitivity and specificity 2, 3
• Ferritin <15 μg/L indicates absent iron stores; <30 μg/L indicates low body iron stores 2, 3
• The combination of low MCV with elevated RDW >14.0% strongly suggests iron deficiency anemia rather than thalassemia minor (which typically has RDW ≤14.0%) 2, 4, 5
• Add transferrin saturation (TSAT) if ferritin appears falsely normal due to inflammation; TSAT <16-20% confirms iron deficiency 2

Critical Pitfall to Avoid

• In the presence of inflammation or infection (which may explain the leukocytosis), ferritin can be falsely elevated up to 100 μg/L despite true iron deficiency 2
• If ferritin is 30-100 μg/L with elevated inflammatory markers, add TSAT to confirm iron deficiency 2

Investigation for Underlying Cause of Iron Deficiency

Mandatory Evaluation

• All adults with confirmed iron deficiency require investigation for the source of blood loss 2, 4
• In men and non-menstruating women with hemoglobin <110 g/L (men) or <100 g/L (women), fast-track gastrointestinal referral is warranted 2
• Upper endoscopy with small bowel biopsies to exclude celiac disease (present in 2-3% of iron deficiency cases) 2
• Colonoscopy to exclude colonic cancer, polyps, and angiodysplasia 2, 4

Additional Considerations

• Screen for malabsorption disorders: celiac disease, H. pylori infection, autoimmune atrophic gastritis 2
• Evaluate for NSAID use, which can cause occult gastrointestinal bleeding 3
• In premenopausal women, assess menstrual blood loss 2

Treatment Algorithm for Iron Deficiency

First-Line Therapy

• Start oral ferrous sulfate 200 mg (65 mg elemental iron) three times daily immediately 2, 4
• Add ascorbic acid (vitamin C) to enhance iron absorption 2, 3
• Continue treatment for at least three months after correction of anemia to replenish iron stores 2, 4

Expected Response and Monitoring

• Hemoglobin should rise ≥10 g/L within 2 weeks if iron deficiency is the cause 2, 3
• Expect hemoglobin increase of at least 2 g/dL within 4 weeks 2, 4
• Monitor hemoglobin and red cell indices at three-monthly intervals for one year, then after a further year 2, 3

Alternative Formulations

• If ferrous sulfate is not tolerated, use ferrous gluconate or ferrous fumarate 2, 3

When to Consider IV Iron

• If patient fails to respond to oral iron within 2-4 weeks, consider intravenous iron if malabsorption is present 2, 3
• Expect hemoglobin increase of at least 2 g/dL within 4 weeks of IV iron 2, 4

Rare Genetic Considerations (If Standard Treatment Fails)

• Consider IRIDA (iron-refractory iron deficiency anemia) if remarkably low TSAT with low-to-normal ferritin and failure to respond to oral iron 2
• IRIDA may respond to intravenous iron (iron sucrose or iron gluconate) 2
• Consider X-linked sideroblastic anemia (ALAS2 defects) with trial of pyridoxine 50-200 mg daily initially, then 10-100 mg daily lifelong if responsive 2
• Genetic testing should be considered with extreme microcytosis (MCV <70), family history of refractory anemia, or failure to respond to adequate iron supplementation 2, 3

Critical Pitfalls to Avoid

• Do not overlook combined deficiencies—iron deficiency can coexist with B12 or folate deficiency, recognizable by elevated RDW 2, 4
• Do not assume all microcytic anemia is iron deficiency—anemia of chronic disease, thalassemia, and sideroblastic anemia require different management 2
• Do not accept esophagitis, erosions, or peptic ulcer as the definitive cause until lower GI tract has been examined 4
• Never ignore the leukocytosis with elevated IG—this requires urgent evaluation to exclude serious infection or malignancy 1