How should I evaluate and manage an adult with mild anemia (Hb (hemoglobin) 11.5 g/dL) and leukopenia (WBC (white blood cell count) 3.3 ×10⁹/L)?

Evaluation and Management of Mild Anemia with Leukopenia

This patient requires immediate iron studies (serum ferritin, transferrin saturation, and C-reactive protein) to confirm iron deficiency anemia, followed by a comprehensive search for the underlying cause—particularly gastrointestinal blood loss or tick-borne illness if there is fever or systemic symptoms. 1, 2

Initial Laboratory Workup

Order the following tests immediately:

• Serum ferritin is the single most specific test for iron deficiency, with levels <15 μg/L confirming absent iron stores and <30 μg/L indicating low body iron stores 1, 2
• Transferrin saturation (TSAT) <16-20% confirms iron deficiency, particularly when ferritin may be falsely elevated by inflammation 1, 2
• C-reactive protein (CRP) to assess for inflammation, which can falsely elevate ferritin 1, 2
• Complete blood count with red cell indices including MCV, MCH, MCHC, and RDW to characterize the anemia 1, 2
• Reticulocyte count to assess bone marrow response 1
• Peripheral blood smear to evaluate for morulae (if tick-borne illness suspected), hypersegmented neutrophils, or other morphologic abnormalities 3, 4

The combination of mild anemia (Hb 11.5 g/dL) and leukopenia (WBC 3.3) raises concern for several conditions:

• Tick-borne rickettsial diseases (ehrlichiosis, anaplasmosis) characteristically present with leukopenia, thrombocytopenia, and mild anemia—particularly if the patient has fever, headache, or recent tick exposure 3
• Iron deficiency anemia with concurrent nutritional deficiency or chronic disease affecting white cell production 1, 2
• Megaloblastic anemia (B12/folate deficiency) can present with pancytopenia including mild anemia and leukopenia 4, 5

Interpretation of Iron Studies

If ferritin <30 μg/L without inflammation:

• This confirms iron deficiency anemia 1, 2
• A cut-off of 45 μg/L provides optimal sensitivity and specificity in routine practice 1, 2

If ferritin 30-100 μg/L with elevated CRP:

• Iron deficiency may still be present despite inflammation falsely elevating ferritin 1, 2
• TSAT <16-20% confirms iron deficiency in this context 1, 2

If ferritin >100 μg/L:

• Absolute iron deficiency is unlikely 2
• Consider anemia of chronic disease (TSAT <20% with ferritin >100 μg/L) 2

Critical Clinical Context Assessment

Evaluate for tick-borne illness if:

• Recent tick exposure (within 2-3 weeks) 3
• Fever, headache, myalgias, nausea, or vomiting 3
• Geographic exposure to endemic areas 3
• If suspected, examine peripheral blood smear for morulae in leukocytes and initiate doxycycline 100 mg every 12 hours immediately without waiting for serologic confirmation, as serology is typically negative in the first week of illness 3

The combination of leukopenia with anemia in ehrlichiosis/anaplasmosis is characteristic, often accompanied by thrombocytopenia and elevated liver enzymes 3

Investigation of Underlying Cause

Once iron deficiency is confirmed, mandatory evaluation includes:

• Gastrointestinal evaluation is essential in adults with confirmed iron deficiency, as occult GI bleeding is the most common cause 1, 2
• Upper endoscopy with duodenal biopsies to exclude celiac disease (present in 2-3% of iron deficiency cases), gastric malignancy, NSAID gastropathy, and peptic ulcer disease 1, 2
• Colonoscopy to exclude colonic carcinoma, polyps, angiodysplasia, and inflammatory bowel disease 1, 2
• Menstrual history in premenopausal women, as heavy menstrual bleeding is a common cause 2
• Dietary assessment for inadequate iron intake, though this alone rarely causes iron deficiency in adults 2
• Medication review for NSAIDs, antiplatelet agents, or anticoagulants that increase bleeding risk 2

Treatment Approach

Initiate oral iron supplementation immediately while diagnostic workup proceeds:

• Ferrous sulfate 325 mg (65 mg elemental iron) 1-3 times daily between meals 1
• Expect hemoglobin increase of 1-2 g/dL every 2-4 weeks with appropriate treatment 1, 4
• A rise in hemoglobin ≥10 g/L within 2 weeks confirms iron deficiency even when iron studies are equivocal 1, 2
• Continue iron for 3-6 months after hemoglobin normalizes to replenish iron stores 1

If patient fails to respond to oral iron within 2-4 weeks, consider:

• Non-compliance with therapy 2
• Ongoing blood loss 2
• Malabsorption (celiac disease, H. pylori, atrophic gastritis) 2
• Switch to intravenous iron if malabsorption confirmed, with expected hemoglobin increase of at least 2 g/dL within 4 weeks 1, 2

Monitoring and Follow-up

• Recheck CBC after 4-8 weeks to confirm hemoglobin rise 1, 4
• Reticulocyte count should increase within 1 week of starting therapy, indicating bone marrow response 4
• Monitor hemoglobin and iron studies at 3-month intervals for the first year 2

Critical Pitfalls to Avoid

• Do not attribute anemia and leukopenia solely to iron deficiency without excluding tick-borne illness, especially with fever or recent tick exposure—ehrlichiosis can be fatal if untreated 3
• Do not delay gastrointestinal investigation in adults with confirmed iron deficiency, as malignancy must be excluded 1, 2
• Do not rely on ferritin alone in inflammatory states, as it can be falsely elevated; add TSAT to confirm iron deficiency 1, 2
• Do not overlook combined deficiencies—iron deficiency can coexist with B12 or folate deficiency, recognizable by elevated RDW 2, 4
• Do not assume dietary insufficiency alone causes iron deficiency in adults; occult bleeding must be excluded 2
• Do not accept upper GI findings (esophagitis, erosions, ulcers) as the sole cause without also examining the lower GI tract, as dual pathology occurs in 10-15% of patients 2