Management of Leukocytosis with Neutrophilia (TLC 20,000 with 66% Neutrophils)
This patient requires immediate evaluation for infection as the primary concern, with targeted antibiotic therapy based on identified source, while ruling out other causes of neutrophilic leukocytosis through clinical assessment and selective testing. 1
Initial Clinical Assessment
Identify the infection source through systematic examination:
- Examine lungs (pneumonia), urinary tract (pyelonephritis), skin/soft tissue (cellulitis/abscess), abdomen (cholecystitis, appendicitis, diverticulitis), indwelling catheters, oropharynx, and perineal region 1, 2
- This neutrophilia pattern (66% neutrophils with WBC 20,000) indicates adequate immune response to infection rather than immunocompromise 1
- The elevated neutrophil-to-lymphocyte ratio suggests acute bacterial infection or inflammatory process 3, 4
Diagnostic Workup
Obtain cultures before initiating antibiotics:
- Draw minimum of two sets of blood cultures, including from any indwelling IV catheters 2
- Order site-specific cultures based on suspected focus: urine culture, sputum culture if productive cough, wound cultures, stool studies if diarrhea present 1, 2
- Obtain chest radiograph if respiratory symptoms are present 2
- Check renal and liver function tests, C-reactive protein, and coagulation screen 2
Management Algorithm
If Infection Source Identified:
- Initiate targeted antibiotic therapy based on suspected source and local resistance patterns 1
- Use broad-spectrum coverage for severe sepsis or septic shock (covering gram-negative and gram-positive organisms) 2
- Duration typically ranges from 5-14 days depending on identified infection 1
- Adjust antibiotics based on culture results and clinical response 1
If No Clear Infection Source:
Consider alternative causes of neutrophilic leukocytosis:
- Recent surgery, exercise, trauma, or emotional stress (can double WBC within hours) 5
- Medications (corticosteroids, lithium, G-CSF) 5
- Smoking, obesity, asplenia 5
- Chronic inflammatory conditions (vasculitis, connective tissue disease, inflammatory bowel disease) 5, 6
- Malignancy (particularly if accompanied by fever, weight loss, bruising, or fatigue) 5
Critical Distinction
This is NOT febrile neutropenia:
- Do not apply febrile neutropenia protocols to this patient 1
- Febrile neutropenia requires ANC <0.5 × 10⁹/L (500 cells/µL), which is the opposite of this presentation 7
- Applying neutropenic fever protocols here leads to unnecessary broad-spectrum antibiotics and hospitalization 1
Common Pitfalls to Avoid
- Do not delay appropriate antibiotics if infection is suspected based on clinical presentation, even while awaiting culture results 1, 2
- Do not assume infection solely based on WBC count - WBC alone has poor discriminative value (AUC 0.54) for bacteremia 3
- Do not overlook non-infectious causes - systemic diseases can produce similar neutrophilia patterns 6
- Repeat CBC with peripheral smear if diagnosis remains unclear, looking for toxic granulations, left shift, or abnormal cell morphology that might suggest hematologic malignancy 5, 8
When to Refer
Refer to hematology/oncology if:
- Malignancy cannot be excluded based on clinical presentation 5
- Peripheral smear shows blasts, immature cells, or other concerning morphology 8
- Persistent unexplained leukocytosis despite treatment of identified infection 5
- Constitutional symptoms (fever, weight loss, night sweats) without identified infection source 5