What is the appropriate workup for a patient with leukocytosis (elevated White Blood Cell count) and fever?

Workup for High WBC and Fever

For a patient with leukocytosis and fever, immediately obtain a chest radiograph, perform a manual differential to assess for left shift (≥16% bands or absolute band count ≥1,500 cells/mm³), and collect blood cultures if bacteremia is suspected, followed by targeted diagnostic testing based on clinical symptoms pointing to respiratory, urinary, abdominal, or skin/soft tissue sources. 1, 2

Temperature Measurement

• Use central temperature monitoring (pulmonary artery catheter thermistors, bladder catheters, or esophageal balloon thermistors) when these devices are already in place 1
• For patients without central monitoring, use oral or rectal temperatures rather than less reliable methods like axillary, tympanic, temporal artery, or chemical dot thermometers 1

Initial Laboratory Assessment

Obtain a complete blood count with manual differential immediately to accurately assess band forms and immature neutrophils, as automated analyzers are insufficient for this critical determination 2, 3

Key Diagnostic Thresholds (in order of diagnostic power):

• Absolute band count ≥1,500 cells/mm³ has the highest likelihood ratio (14.5) for bacterial infection 2, 4
• Neutrophil percentage >90% has a likelihood ratio of 7.5 for bacterial infection 2, 4
• Left shift (≥16% band neutrophils) has a likelihood ratio of 4.7 for bacterial infection, even with normal total WBC 2, 3
• Total WBC ≥14,000 cells/mm³ has a likelihood ratio of only 3.7 for bacterial infection 2, 4

Critical pitfall: Do not ignore a left shift when total WBC is normal—this combination still indicates significant bacterial infection requiring full evaluation 3

Imaging Studies

Chest Imaging (Mandatory):

• Perform a chest radiograph on all patients who develop fever during ICU stay or present with fever and leukocytosis 1
• If chest radiograph is abnormal and sufficient expertise is available, perform thoracic bedside ultrasound to more reliably identify pleural effusions and parenchymal or interstitial lung pathology 1

Abdominal Imaging:

• Do NOT routinely perform abdominal ultrasound or POCUS in patients without abdominal signs, symptoms, liver function abnormalities, or recent abdominal surgery 1
• Perform formal bedside diagnostic ultrasound of the abdomen if the patient has recent abdominal surgery, abdominal symptoms, abnormal physical examination/POCUS, or elevated transaminases, alkaline phosphatase, or bilirubin 1

Advanced Imaging for Unclear Etiology:

• For patients with recent thoracic, abdominal, or pelvic surgery where initial workup fails to identify an etiology, perform CT in collaboration with the surgical service 1
• Consider 18F-fluorodeoxyglucose PET/CT if other diagnostic tests have failed and transport risk is acceptable 1

Targeted Diagnostic Testing Based on Clinical Symptoms

Respiratory Symptoms:

• Obtain pulse oximetry and chest radiography if hypoxemia is documented 3
• Consider thoracic ultrasound if chest radiograph is abnormal 1

Urinary Symptoms (dysuria, gross hematuria, new incontinence):

• Perform urinalysis for leukocyte esterase/nitrite and microscopic examination for WBCs 3
• If pyuria is present, obtain urine culture 3

Skin/Soft Tissue Findings:

• Consider needle aspiration or deep-tissue biopsy if unusual pathogens are suspected, fluctuant areas are present, or initial treatment is unsuccessful 3

Gastrointestinal Symptoms:

• Evaluate volume status and examine stool for pathogens, including C. difficile, if colitis symptoms are present 3

Blood Cultures

Obtain blood cultures only if bacteremia is highly suspected clinically, quick laboratory access is available, adequate physician coverage is present, and capacity to administer parenteral antibiotics exists 3

Special Considerations

Older Adults:

• In older adults in long-term care facilities, typical symptoms and signs of infection are frequently absent, and basal body temperature decreases with age and frailty 2
• Left shift has particular diagnostic importance in this population due to these atypical presentations 3

Non-Infectious Causes to Consider:

• Medications (lithium, beta-agonists, epinephrine, corticosteroids) can cause leukocytosis 4, 5, 6
• Physical stress (surgery, exercise, trauma), emotional stress, smoking, obesity, and chronic inflammatory conditions can elevate WBC 5, 6
• Myelodysplastic syndromes can show left shift as a dysplastic feature 3

Red Flags for Hematologic Malignancy:

• Extremely elevated WBC counts (>100,000/mm³ represents a medical emergency) 6
• Concurrent abnormalities in red blood cell or platelet counts 5, 6
• Weight loss, bruising, bleeding, or hepatosplenomegaly 5, 6
• If malignancy cannot be excluded, refer to hematology/oncology 5

Common Pitfalls to Avoid

• Do not rely on automated analyzer flags alone—manual differential is essential for accurate band assessment 2, 3
• Do not ignore left shift when total WBC is normal—this combination still indicates significant bacterial infection 2, 3
• Do not treat based solely on laboratory findings—correlate with clinical presentation, fever patterns, and specific infection symptoms 2, 3
• Do not perform routine abdominal imaging without abdominal signs, symptoms, or recent surgery 1