Role of Complete Blood Count (CBC) in Diagnosing Fatigue and Infection
A CBC with differential should be obtained when infection is suspected based on clinical presentation (fever, localized symptoms, acute onset) or when evaluating unexplained fatigue, but not as routine screening in asymptomatic patients. 1
When to Order CBC for Suspected Infection
Order CBC with differential within 12-24 hours of symptom onset when patients present with:
- Fever patterns: Temperature >100°F (37.8°C), >2 readings of >99°F (37.2°C), or increase of 2°F (1.1°C) over baseline 1
- Acute onset symptoms: Dysuria, gross hematuria, new/worsening incontinence (UTI), respiratory symptoms (pneumonia), or severe gastrointestinal symptoms persisting >7 days 1
- Clinical signs of focal infection: Localized pain, tenderness, erythema, or organ-specific symptoms 2
Manual differential is preferred over automated differential to accurately assess bands and other immature white blood cell forms 1
Interpreting CBC Results for Infection
High-Yield Indicators of Bacterial Infection
The following CBC findings have strong diagnostic value for bacterial infection:
- Elevated total band neutrophil count ≥1,500 cells/mm³: Likelihood ratio 14.5 for bacterial infection 2
- Left shift (≥16% band neutrophils): Likelihood ratio 4.7 for bacterial infection 2
- WBC count ≥14,000 cells/mm³: Likelihood ratio 3.7 for bacterial infection, warrants careful assessment even without fever 1, 3
- Neutrophil percentage >90%: Likelihood ratio 7.5 for bacterial infection 2
Important Caveat About Normal WBC
Do not rely solely on normal total WBC count to rule out infection. 1 Even with normal total WBC, evaluate the differential for left shift, which may indicate bacterial infection despite normal counts 1. In older adults particularly, typical symptoms and signs of infection are frequently absent, making CBC interpretation more challenging 1.
When to Order CBC for Fatigue
Order CBC when evaluating fatigue to detect:
- Anemia: Assess hemoglobin, hematocrit, MCV, and RDW 4, 5
- Leukopenia or thrombocytopenia: Common in HIV-infected persons and other chronic conditions 4
- Inflammatory markers: Elevated WBC may indicate underlying infection or inflammatory disease 6
The CBC is used alongside chemistry panel to assess renal and hepatic function and nutritional status in patients with chronic fatigue 4.
Critical Pitfalls to Avoid
- Do not order routine or scheduled CBCs in asymptomatic patients: This leads to unnecessary costs and potential false positives 1
- Do not order CBCs when results will not change management decisions 1
- Do not overlook absolute neutrophil count elevation when total WBC is only mildly elevated 2
- Do not treat asymptomatic patients with antibiotics based solely on mildly elevated neutrophil counts 2
- In older adults, do not rely on classic fever definitions: Basal body temperature decreases with age and frailty 1
When CBC Results Do Not Require Further Testing
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, 2. Clinical symptoms and signs should guide further evaluation when WBC count is within normal range 1.
Special Clinical Situations
HIV-Infected Patients
CBC with differential and chemistry panel should be obtained upon initiation of care, as anemia, leukopenia, and thrombocytopenia are common 4. The CBC is also used to calculate total CD4 lymphocyte count 4.
Renal Stone Disease with Infection
WBC elevation >11 × 10^9/L along with elevated C-reactive protein may indicate complications such as infection associated with obstruction 3. WBC count >14,000 cells/mm³ warrants assessment for bacterial infection, and urgent decompression may be necessary if sepsis is suspected 3.
Patients with Cirrhosis
In cirrhosis patients with ascites, altered WBC count may indicate spontaneous bacterial peritonitis requiring diagnostic paracentesis 2. Neutrophil count >250 cells/mm³ in ascitic fluid indicates spontaneous bacterial peritonitis requiring immediate antibiotic treatment 2.