Can white blood cell (WBC) count decrease in infection?

Can WBC Fall During Infection?

Yes, white blood cell (WBC) count can definitely decrease during infection, and this phenomenon occurs through multiple mechanisms and clinical scenarios that require careful recognition.

When and Why WBC Falls in Infection

Neutropenic Patients with Infection

• In neutropenic patients, WBC count cannot be used as a criterion to define sepsis because these patients lack the ability to mount a leukocytosis response 1.
• Approximately 50-60% of febrile neutropenic patients have an established or occult infection despite their low WBC count 1.
• The absence of granulocytes means signs and symptoms of infection are often absent or muted, though fever remains an early sign 1.

Early Phase of Bacterial Infection

• In the initial 0-10 hours after onset of bacterial infection, WBC count can decrease below the reference range without left shift 2.
• This is followed by a second phase (10-20 hours) where low WBC count continues but left shift appears 2.
• Only later (one to several days) does WBC count increase above reference range with left shift 2.

Severe Infections

• Leukopenia (WBC ≤3,000 cells/μL) occurs in severe infections and is associated with higher APACHE II scores (18 vs 12, p<0.0001) 3.
• Leukopenic patients with infection have higher mortality rates (23.7% vs 11.4%, p=0.004), though this reflects disease severity rather than the leukopenia itself being an independent predictor 3.

Specific Viral Infections

• Influenza A commonly causes low WBC count in children, with lymphopenia (<1.5 in 41%, <1.0 in 40%) 1.
• In H5N1 cases, all seven children had WBC <4.0 (mean 2.44) and 6/7 had lymphopenia <1.0 (mean 0.66), with six of seven dying 1.
• A raised WBC (>15) is found in only 8-12% of influenza cases 1.

Clinical Mechanisms

Increased Utilization and Destruction

• Leukopenia results from either reduced production of white blood cells or increased utilization and destruction, or both 4.
• Infection itself can cause increased utilization and destruction of WBCs, particularly in overwhelming sepsis 4.

Bone Marrow Suppression

• The rate of decline of neutrophil count and duration of neutropenia are critical factors highly correlated with severity of infection and clinical outcome 1.

Critical Clinical Implications

Recognition of Severe Illness

• Although very low WBC counts represent markers of severe illness in infected patients, they do not appear to be independent contributors to worsened outcome 3.
• The major danger of neutropenia is the risk of infection itself, requiring identification of the cause and effective antimicrobial therapy 4.

Diagnostic Approach in Leukopenic Infection

• Fever remains an early sign even when WBC cannot rise 1.
• Focus on other inflammatory parameters: C-reactive protein, procalcitonin (>2 SD above normal), fever (>38.3°C), hypothermia (<36°C), tachycardia, tachypnea 1.
• Blood cultures should be obtained, as 10-20% of patients with neutrophil counts <100/μL will develop bloodstream infection 1.

Common Pitfalls to Avoid

• Do not assume absence of infection based on low or normal WBC count - bacterial infections can present with leukopenia, particularly in early phases or severe disease 2, 1.
• Do not delay antibiotics in neutropenic patients awaiting WBC rise - these patients cannot mount a leukocytosis response 1.
• Recognize that low WBC in viral infections (especially influenza) is common and expected, not a sign of bacterial superinfection unless other criteria are met 1.
• In children with influenza, leukopenia and lymphopenia are the norm, not the exception 1.