Is a complete blood count (CBC) with differential a reasonable initial test in a patient presenting with fever?

CBC with Differential in Febrile Patients: A Reasonable Initial Test

Yes, a CBC with differential is a reasonable and often essential initial test in patients presenting with fever, particularly when infection is suspected based on clinical presentation, though it should not be used as routine screening in asymptomatic individuals. 1

When CBC with Differential is Indicated

The most important principle: Order CBC with differential when infection is suspected based on clinical symptoms, not as a screening test. 1

Specific Clinical Scenarios Requiring CBC:

• Fever with nonspecific symptoms - When the differential diagnosis includes viral syndrome, bacterial infection, or other systemic illness, CBC should be ordered to help guide diagnosis 2
• Critically ill ICU patients with new fever - CBC with manual differential is part of the standard fever workup when etiology is not readily identified 2
• Fever with specific organ symptoms - When respiratory symptoms (cough, dyspnea), urinary symptoms (dysuria, hematuria), or altered mental status accompany fever 1, 3
• High-risk patients - Those with heart disease, diabetes, or respiratory disease who develop fever warrant CBC testing due to elevated risk of severe complications 4

Critical Technical Requirements

Always request a manual differential, not just automated counts. The manual differential is strongly preferred because it accurately assesses band forms and other immature neutrophils that automated analyzers miss 1, 3. This distinction is clinically crucial because:

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

Timing of Testing

• Complete testing within 12-24 hours of symptom onset, or sooner if the patient is seriously ill 1
• Results should guide immediate management decisions, including whether to initiate empiric antibiotics or pursue additional diagnostic testing 2, 3

Interpreting CBC Results in Context

Critical caveat: Leukocytosis and elevated WBC alone are insufficient to diagnose infection and must be interpreted alongside clinical symptoms, fever patterns, and signs of focal infection. 4

When CBC Suggests Bacterial Infection:

• Elevated WBC (≥14,000 cells/mm³) with left shift and clinical symptoms pointing to a specific source warrants targeted diagnostic testing 4, 3
• Obtain blood cultures if bacteremia is suspected 3
• Perform chest radiograph for respiratory symptoms 3
• Order urinalysis with culture for urinary symptoms 3
• Consider abdominal ultrasound if abdominal symptoms or liver function abnormalities present 2

When CBC is Normal or Equivocal:

• In the absence of fever, normal WBC count, no left shift, AND no specific clinical manifestations of focal infection, additional diagnostic tests may not be indicated due to low potential yield 1, 4
• However, even with normal total WBC, assess the differential carefully - left shift can indicate bacterial infection despite normal total count 1
• Consider procalcitonin (PCT) or C-reactive protein (CRP) if probability of bacterial infection is low to intermediate 2

Special Populations: Older Adults

In older adults, particularly those in skilled nursing facilities, CBC interpretation requires modified thresholds and heightened clinical suspicion. 1

• Typical symptoms and signs of infection are frequently absent 1, 3
• Basal body temperature decreases with age and frailty, making classic fever definitions less reliable 1
• Use modified fever definitions: >100°F (37.8°C), ≥2 readings >99°F (37.2°C), or 2°F (1.1°C) increase from baseline 1, 4
• Left shift has particular diagnostic importance in older adults due to atypical presentations 4, 3
• Review advance directives before ordering any testing 1

Common Pitfalls to Avoid

• Do not order routine or scheduled CBC testing in asymptomatic patients - this leads to unnecessary costs and false positives 1
• Do not rely solely on CBC results to rule out infection - clinical correlation is mandatory 1
• Do not order CBC when results will not change management decisions 1
• Do not accept automated differential alone - insist on manual differential for accurate band assessment 1, 3
• Do not interpret WBC count in isolation - the differential (especially bands) often provides more diagnostic value than total WBC 4, 3

Algorithmic Approach to CBC Ordering in Fever

1. Assess clinical presentation: Does the patient have specific symptoms suggesting focal infection (respiratory, urinary, abdominal, skin/soft tissue)? 4, 3
2. Verify fever using appropriate definitions for patient's age and setting 1, 3
3. If infection suspected clinically: Order CBC with manual differential 1, 3
4. Interpret results in context:
   • High WBC + left shift + clinical symptoms = pursue targeted diagnostics 4, 3
   • Normal WBC but left shift present + clinical symptoms = still pursue infection workup 1
   • Normal WBC, no left shift, no focal symptoms = consider observation or alternative diagnoses 1, 4
5. Only perform tests that have reasonable diagnostic yield, are low risk, reasonable in cost, and will improve patient management 1