Which medications can cause leukocytosis in a 78‑year‑old woman with mild leukocytosis (white blood cell count 10.9 ×10⁹/L, absolute neutrophil count 8,415/µL)?

Medications That Cause Leukocytosis

Corticosteroids, lithium, and beta-agonists are the most commonly implicated medications causing leukocytosis, with corticosteroids being the most frequent culprit in clinical practice. 1

Primary Medication Classes Associated with Leukocytosis

Corticosteroids (Most Common)

• Corticosteroids are the leading medication cause of leukocytosis, producing neutrophilia through multiple mechanisms including demargination of neutrophils from vessel walls and reduced neutrophil apoptosis 1
• The white blood cell count can double within hours after corticosteroid administration due to mobilization from large bone marrow storage pools and intravascularly marginated neutrophil pools 2
• This effect occurs with both systemic and high-dose inhaled corticosteroids 1

Lithium

• Lithium consistently causes leukocytosis through stimulation of granulocyte colony-stimulating factor production 1
• The elevation is typically mild to moderate and persists throughout treatment 1

Beta-Agonists

• Beta-adrenergic agonists (such as albuterol, terbutaline) cause leukocytosis primarily through demargination of neutrophils 1
• This effect is usually transient and dose-dependent 2

Additional Medications Causing Leukocytosis

Chemotherapy Agents (Paradoxical Effect)

• Hydroxyurea, while used to reduce white blood cell counts in myeloproliferative disorders, can paradoxically cause initial leukocytosis before achieving cytoreduction 3
• All-trans retinoic acid (ATRA) causes differentiation syndrome with marked leukocytosis, particularly in acute promyelocytic leukemia patients, requiring cytoreductive therapy when WBC exceeds 10 × 10⁹/L 3

Growth Factors

• Granulocyte colony-stimulating factor (G-CSF) therapeutically increases neutrophil counts and is used to treat neutropenia, but represents an iatrogenic cause of leukocytosis 3
• Erythropoietin-stimulating agents can occasionally cause reactive leukocytosis 3

Clinical Context for Your 78-Year-Old Patient

For a 78-year-old woman with WBC 10.9 × 10⁹/L and ANC 8,415/µL, this represents only mild leukocytosis that does not require intervention unless symptomatic. 2

Assessment Framework

• This WBC count (10.9 × 10⁹/L) is only marginally elevated and falls within the range commonly seen with physiologic stress, medications, or chronic inflammatory conditions 2, 1
• The absolute neutrophil count of 8,415/µL indicates neutrophilic predominance, consistent with medication effect, stress response, or chronic inflammation rather than malignancy 2

Medication Review Priority

Review the patient's medication list specifically for:

• Any corticosteroid use (prednisone, methylprednisolone, dexamethasone, inhaled steroids at high doses) 1
• Lithium for psychiatric conditions 1
• Beta-agonists (albuterol, salmeterol) for respiratory conditions 1
• Recent G-CSF administration 3

Non-Medication Causes to Consider

• Physical or emotional stress from recent surgery, trauma, or acute illness can double the WBC count within hours 2, 1
• Smoking causes chronic mild leukocytosis 2
• Obesity is associated with chronic low-grade elevation in WBC 2
• Chronic inflammatory conditions (rheumatoid arthritis, inflammatory bowel disease) 2

Critical Red Flags Requiring Urgent Evaluation

Immediate hematology referral is indicated if any of the following are present:

• WBC count >100 × 10⁹/L, which represents a medical emergency due to risk of brain infarction and hemorrhage 1
• Constitutional symptoms: fever, unintentional weight loss, night sweats, or fatigue 2, 1
• Concurrent cytopenias: anemia or thrombocytopenia suggesting bone marrow disorder 1
• Organomegaly: splenomegaly, hepatomegaly, or lymphadenopathy 1
• Abnormal peripheral smear showing blasts, immature cells, or dysplasia 4

Management Approach for Mild Leukocytosis

For this patient's mild elevation (WBC 10.9 × 10⁹/L), the recommended approach is:

• Repeat CBC with differential in 2-4 weeks to determine if this is transient or persistent 2
• Review and document all current medications, particularly those listed above 1
• Assess for infection with history, physical examination, and inflammatory markers if clinically indicated 2, 1
• Peripheral blood smear examination if the leukocytosis persists or worsens, to evaluate cell morphology and maturity 2, 4

When to Escalate Care

• Persistent leukocytosis >15 × 10⁹/L without identified reversible cause warrants peripheral smear and possible hematology consultation 2, 1
• Any WBC >20 × 10⁹/L should prompt peripheral smear examination to exclude malignancy 4
• Development of symptoms (fever, weight loss, bruising, fatigue) requires immediate further evaluation 2

Common Pitfalls to Avoid

• Do not assume leukocytosis is benign without reviewing the peripheral smear when counts are persistently elevated or rising 4
• Do not overlook medication-induced leukocytosis as corticosteroids are ubiquitous and often not considered by patients as "real medications" 1
• Do not delay evaluation if constitutional symptoms are present, even with mild leukocytosis, as chronic leukemias often present incidentally with minimal symptoms 1
• Do not order extensive workup for transient mild leukocytosis in the setting of acute stress, infection, or recent medication changes—repeat testing is more appropriate 2