How should a patient with hypochromic microcytic anemia, leukocytosis, and low iron saturation be managed?

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Laboratory Interpretation and Management

This patient does NOT have anemia—the hemoglobin of 154 g/L is well above the WHO threshold of 130 g/L for men and 120 g/L for non-pregnant women, and the elevated MCHC (316 g/L) indicates hypochromia suggesting early iron deficiency without anemia, combined with mild leukocytosis that warrants investigation for underlying inflammation or infection. 1

Key Laboratory Findings

Hemoglobin and Hematocrit Status:

  • Hemoglobin 154 g/L and hematocrit 0.49 are both normal to high-normal values, definitively excluding anemia by WHO criteria 1
  • The RBC count of 5.64 × 10¹²/L is also within normal range 1

Iron Status Indicators:

  • MCHC of 316 g/L indicates hypochromia (reduced hemoglobin concentration in red cells), which is a marker of iron deficiency that may be more reliable than MCV alone 1
  • Iron saturation of 0.23 (23%) is borderline low, as transferrin saturation <20% typically indicates iron deficiency, though values between 20-25% warrant further evaluation 1
  • This pattern suggests non-anemic iron deficiency (NAID)—depleted iron stores without yet developing anemia 1

Leukocytosis:

  • WBC 12.3 × 10⁹/L with neutrophils 9.2 × 10⁹/L represents mild leukocytosis with neutrophilia, suggesting possible inflammation, infection, or physiologic stress 1
  • This inflammatory state is clinically important because inflammation can mask iron deficiency by elevating ferritin levels (an acute phase reactant) 1

Diagnostic Approach

Essential Next Steps:

  • Obtain serum ferritin immediately as it is the single most useful marker for confirming iron deficiency 1

    • Ferritin <15 μg/L is highly specific for iron deficiency (specificity 0.99) 1
    • Ferritin <30 μg/L generally indicates low iron stores 1
    • However, if ferritin is 30-100 μg/L in the context of inflammation (suggested by the leukocytosis), this may represent a "false-normal" ferritin masking true iron deficiency 1
    • Ferritin <45 μg/L provides optimal sensitivity/specificity trade-off for iron deficiency, especially with concurrent inflammation 1
  • Calculate MCV (mean corpuscular volume) from the available data to assess for microcytosis, though MCH (mean corpuscular hemoglobin) would be more reliable if available 1

  • Investigate the cause of leukocytosis:

    • Rule out acute infection (clinical examination, inflammatory markers like CRP) 1
    • Consider chronic inflammatory conditions that could cause both iron sequestration and leukocytosis 1, 2

Management Strategy

If Iron Deficiency is Confirmed (ferritin <30-45 μg/L):

  • In non-anemic iron deficiency without GI symptoms, investigation for GI pathology is generally NOT warranted, particularly in premenopausal women where menstrual losses are the likely cause 1
  • However, the presence of leukocytosis changes this calculus—investigate for underlying chronic inflammatory conditions, infections, or occult malignancy that could explain both findings 1

Iron Supplementation:

  • Oral iron therapy is first-line treatment: ferrous sulfate 324 mg (65 mg elemental iron) daily 3, 4
  • Monitor response at 2 weeks: hemoglobin rise ≥10 g/L confirms iron deficiency even if initial iron studies were equivocal 1
  • Continue supplementation to replete iron stores, not just correct hemoglobin 4

If Inflammation is Present (elevated CRP, persistent leukocytosis):

  • Oral iron may be ineffective due to hepcidin-mediated blockade of iron absorption in inflammatory states 1, 2
  • Consider intravenous iron if oral therapy fails or if there is evidence of functional iron deficiency with inflammation 1, 5
  • Treat the underlying inflammatory condition as this is essential for effective iron utilization 1, 2, 6

Critical Pitfalls to Avoid

  • Do not assume anemia is present—this patient's hemoglobin is normal; the issue is iron deficiency without anemia 1
  • Do not ignore the leukocytosis—this suggests inflammation that could both mask iron deficiency (via elevated ferritin) and impair response to oral iron 1, 2
  • Do not perform extensive GI investigation for non-anemic iron deficiency in the absence of other concerning features, as the yield for serious pathology is low 1
  • Do not use ferritin alone in the context of inflammation—transferrin saturation and clinical context are essential for accurate interpretation 1

References

Guideline

Guideline Directed Topic Overview

Dr.Oracle Medical Advisory Board & Editors, 2025

Research

[Diagnosis and treatment of iron deficiency anemia].

[Rinsho ketsueki] The Japanese journal of clinical hematology, 2024

Research

Anemia of chronic disease: pathophysiology and laboratory diagnosis.

Laboratory hematology : official publication of the International Society for Laboratory Hematology, 2005

Professional Medical Disclaimer

This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.

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