What is leukocytosis?

What is Leukocytosis

Leukocytosis is an elevated white blood cell (WBC) count above 11,000 cells/mm³ in nonpregnant adults, most commonly caused by infections, inflammatory processes, medications, or physical/emotional stress, though primary bone marrow disorders must be excluded when counts are markedly elevated or accompanied by other hematologic abnormalities. 1, 2, 3

Definition and Thresholds

• Standard definition: WBC count >11,000 cells/mm³ in nonpregnant adults 2, 3
• Clinically significant threshold in older adults: WBC count ≥14,000 cells/mm³, which has a likelihood ratio of 3.7 for bacterial infection 4
• Medical emergency threshold: WBC count >100,000 cells/mm³ (hyperleukocytosis) due to risk of brain infarction and hemorrhage from leukostasis 4, 1

Age-specific and pregnancy-specific normal ranges must be used, as normal WBC counts vary across populations 2.

Common Causes

Benign/Secondary Causes (Most Common)

Infections and inflammation are the most frequent causes of leukocytosis, triggering a normal bone marrow response with increased polymorphonuclear leukocytes and immature forms (left shift) 1, 2.

• Bacterial infections: Produce neutrophilic leukocytosis with left shift 4, 1
• Physical stress: Surgery, exercise, trauma, seizures, anesthesia can double WBC count within hours due to release from bone marrow storage pools 1, 2
• Emotional stress: Can elevate WBC counts 1
• Medications: Corticosteroids, lithium, beta-agonists, epinephrine are commonly implicated 5, 1, 2
• Chronic conditions: Obesity, smoking, asplenia, chronic inflammatory diseases 2, 6
• Allergic/parasitic conditions: Cause eosinophilia leading to leukocytosis 1, 2

Malignant/Primary Bone Marrow Disorders (Less Common but Serious)

Primary bone marrow disorders should be suspected when WBC counts are extremely elevated, when there are concurrent abnormalities in red blood cells or platelets, or when constitutional symptoms are present. 1, 2, 3

• Acute leukemias: Patients typically appear ill at presentation with severe symptoms of rapid onset 1, 3
• Chronic leukemias: Often diagnosed incidentally on routine blood work, with gradual symptom onset 1, 3, 6
• Myeloproliferative disorders: Include chronic myeloid leukemia (CML), which can present with marked leukocytosis 4, 6

Clinical Assessment Algorithm

Red Flags Requiring Urgent Evaluation

• Constitutional symptoms: Fever, weight loss, night sweats, fatigue 2, 3
• Bleeding or bruising: Suggests platelet dysfunction or thrombocytopenia 1, 2
• Organomegaly: Enlarged liver, spleen, or lymph nodes 1, 2
• Concurrent cytopenias: Anemia or thrombocytopenia alongside leukocytosis 1, 2
• Extreme elevation: WBC >100,000 cells/mm³ requires emergency management 4, 1

Initial Diagnostic Approach

Obtain a complete blood count with manual differential to assess cell types, maturity, and presence of abnormal forms—automated analyzers are insufficient for accurate assessment 4, 5, 7.

• Evaluate the differential: Neutrophilia suggests bacterial infection, eosinophilia suggests parasitic/allergic causes, lymphocytosis suggests viral illness (especially in children) 1, 2
• Assess for left shift: Band neutrophils ≥16% (likelihood ratio 4.7) or absolute band count ≥1,500 cells/mm³ (likelihood ratio 14.5) strongly suggests bacterial infection 4, 5
• Review peripheral smear: Look for immature cells (blasts), toxic granulations, uniformity of cells, and dysplastic features 1, 2, 3
• Correlate with clinical context: Identify signs/symptoms of infection (fever, cough, dysuria, wound drainage) or systemic illness 7, 2

When to Suspect Malignancy

Refer urgently to hematology/oncology if:

• Peripheral smear shows blasts or immature cells 2, 3
• Constitutional symptoms cannot be explained by infection 2, 3
• Concurrent unexplained anemia or thrombocytopenia 1, 2
• Persistent leukocytosis without clear infectious or inflammatory cause 8, 2
• WBC >100,000 cells/mm³ (hyperleukocytosis) 4, 1

Special Clinical Contexts

Hyperleukocytosis (WBC >100,000 cells/mm³)

This represents a medical emergency requiring immediate intervention due to risk of leukostasis causing cerebral or pulmonary complications 4, 1.

• Immediate management: Hydroxyurea 50-60 mg/kg/day until WBC <10-20 × 10⁹/L 4
• Consider leukapheresis: For initial management, though no long-term outcome benefit proven 4
• Avoid excessive transfusions: Can increase blood viscosity and worsen leukostasis 4
• Prevent tumor lysis syndrome: Hydration, allopurinol or rasburicase, monitor uric acid and electrolytes 4

Persistent Unexplained Leukocytosis

Patients with prolonged leukocytosis without clear infection may have persistent inflammation-immunosuppression and catabolism syndrome (PICS), characterized by extensive tissue damage rather than active infection 8.

• Common in: Major trauma, sepsis, cerebrovascular accidents, major surgery 8
• Associated findings: Prolonged bandemia, later development of eosinophilia (>500 cells/mm³), colonization with resistant organisms 8
• Avoid prolonged empiric antibiotics: Unless clear infection documented, as this increases risk of C. difficile and resistant organisms 8

Common Pitfalls to Avoid

• Do not rely on automated differential alone: Manual review is essential for accurate assessment of immature forms and left shift 4, 5, 7
• Do not ignore left shift with normal total WBC: This combination still indicates significant bacterial infection requiring evaluation 4, 5, 7
• Do not overlook medication causes: Review corticosteroids, lithium, beta-agonists before extensive workup 5, 1, 2
• Do not delay hematology referral: When peripheral smear is abnormal or constitutional symptoms present 2, 3
• Do not treat with prolonged empiric antibiotics: Without documented infection, especially in persistent leukocytosis from tissue damage 8