What is the diagnosis and treatment for a patient with leukocytosis, microcytic anemia, and elevated RDW?

Diagnosis: Iron Deficiency Anemia with Reactive Leukocytosis

This patient has iron deficiency anemia (IDA) based on the microcytic anemia (MCV 70 fL, hemoglobin 10.7 g/dL) with elevated RDW (15.7%), and the leukocytosis (WBC 11.6) with neutrophilia (7.4) is most likely reactive rather than a primary hematologic malignancy. 1

Laboratory Interpretation

Anemia Classification

• The hemoglobin of 10.7 g/dL confirms anemia (WHO defines anemia as <13 g/dL in men, <12 g/dL in women), and the MCV of 70 fL indicates microcytic anemia (MCV <80 fL). 1
• The elevated RDW of 15.7% strongly supports iron deficiency as the cause of microcytosis, with sensitivity of 77% for IDA and specificity of 91%. 2
• The MCHC of 21.4 g/dL is abnormally low (normal 32-36 g/dL), further confirming hypochromic microcytic anemia characteristic of iron deficiency. 1

Leukocytosis Assessment

• The WBC of 11.6 with neutrophils 7.4 and lymphocytes 3.3 represents mild leukocytosis with neutrophil predominance, which is commonly reactive in the setting of iron deficiency anemia rather than indicative of leukemia. 3
• Leukocytosis in the context of anemia without blast cells or other concerning features does not suggest acute leukemia, which would typically present with more dramatic WBC elevations, circulating blasts, and other cytopenias. 3

Differential Diagnosis

Primary Diagnosis: Iron Deficiency Anemia

• Iron deficiency is the most likely diagnosis given the combination of microcytosis (MCV 70), elevated RDW (15.7%), and hypochromia (low MCHC). 1
• RDW elevation occurs early in iron deficiency, even before significant anemia develops, and increases progressively with worsening deficiency. 2

Alternative Considerations

• Thalassemia trait is less likely because while it causes microcytosis, it typically presents with normal or only mildly elevated RDW (mean 15.76 ± 1.41% in beta-thalassemia trait versus 20.62 ± 4.64% in IDA). 4
• However, nearly half of thalassemia cases can have elevated RDW, so thalassemia cannot be definitively excluded without hemoglobin electrophoresis. 5
• Combined iron deficiency and thalassemia trait would present similarly to isolated IDA with markedly elevated RDW. 4

Recommended Diagnostic Workup

Essential Initial Tests

• Serum ferritin is the most sensitive marker for iron stores and should be measured first, with <30 μg/L indicating iron deficiency in non-inflammatory states. 1
• Transferrin saturation <20% indicates functional or absolute iron deficiency and should be obtained alongside serum iron and total iron binding capacity. 1
• C-reactive protein (CRP) should be measured because inflammatory conditions alter ferritin interpretation, and ferritin 30-100 μg/L with inflammation may still indicate iron deficiency. 1

Secondary Evaluation

• Hemoglobin electrophoresis should be performed if iron studies are normal or equivocal to evaluate for thalassemia trait, particularly given the severe microcytosis (MCV 70). 1
• Reticulocyte count helps distinguish production defects from hemolysis or blood loss, though in IDA it is typically low or inappropriately normal. 1
• Investigation for source of blood loss is mandatory once iron deficiency is confirmed, including gastrointestinal evaluation in adults. 1

Treatment Approach

Iron Replacement Therapy

• Oral iron supplementation is first-line treatment once iron deficiency is confirmed, typically ferrous sulfate 325 mg (65 mg elemental iron) two to three times daily. 3
• Iron status should be monitored during treatment to assess response and detect any complications. 3
• RDW may transiently increase during the first month of iron therapy before normalizing, which should not be misinterpreted as treatment failure. 4

Addressing Underlying Cause

• The source of iron loss must be identified and treated, as iron deficiency in adults is blood loss until proven otherwise. 1
• Gastrointestinal evaluation is essential in the absence of obvious menstrual or other bleeding sources. 1

Clinical Pitfalls to Avoid

Common Diagnostic Errors

• Do not assume leukocytosis indicates leukemia without examining the peripheral smear for blasts and assessing for other cytopenias or clinical features of malignancy. 3
• Do not rely solely on MCV for classification, as coexisting conditions may neutralize MCV changes, and elevated RDW is critical for distinguishing causes. 1, 5
• Do not misinterpret ferritin without considering inflammatory status, as ferritin is an acute phase reactant and may be falsely elevated in inflammation. 1

Treatment Considerations

• Do not fail to investigate the underlying cause of iron deficiency, as simply replacing iron without addressing blood loss leads to recurrence. 1
• Monitor for iron overload if transfusions or excessive supplementation is given, though this is uncommon with oral therapy alone. 3