Why can a normal white blood cell (WBC) count be observed in orthopaedic infection cases?

Why White Blood Cell Count Can Be Normal in Orthopaedic Infections

Peripheral white blood cell (WBC) counts are not elevated in most patients with orthopaedic infections, making a normal WBC count essentially meaningless for excluding or confirming infection. 1, 2

The Fundamental Problem with Peripheral WBC Counts

The peripheral WBC count is an unreliable marker for orthopaedic infections because:

• Peripheral leukocyte counts remain normal in the majority of patients with infected prostheses, despite active infection 1
• Even in documented bacterial infections among older persons, approximately 50% present without fever or leukocytosis 1
• Only 37% of patients with proven infections had WBC counts >20×10⁹ cells/L, and just 50% exceeded 15×10⁹ cells/L 1
• The absence of systemic leukocytosis does not exclude localized bone or joint infection 1

Why Local Infection Doesn't Always Cause Systemic WBC Elevation

Compartmentalized Inflammatory Response

Orthopaedic infections, particularly chronic or low-grade infections, often remain localized to the bone, joint, or periprosthetic space without triggering a robust systemic inflammatory response 1. The infection may be:

• Contained within the joint capsule or bone, preventing widespread systemic activation 1
• Chronic and indolent, especially with low-virulence organisms like coagulase-negative Staphylococcus species 1
• Biofilm-associated in prosthetic joint infections, which elicits minimal systemic immune response 1

Patient-Specific Factors

Certain populations are particularly prone to normal WBC counts despite infection:

• Immunocompromised patients (29% of one cohort) may lack the ability to mount leukocytosis 3
• Elderly patients often have blunted immune responses 1
• Patients with neutropenia cannot generate elevated WBC counts by definition 1

What Actually Works: Superior Diagnostic Markers

C-Reactive Protein (CRP)

CRP demonstrates 73-91% sensitivity and 81-86% specificity for prosthetic knee infection using a cutoff of 13.5 mg/L, making it far more reliable than peripheral WBC count 1, 2, 4. CRP:

• Rises within 12-24 hours after infection onset and peaks at 48 hours 4
• Is less affected by confounding factors like anemia and azotemia that artificially alter ESR 4
• Returns to baseline within 2 months after uncomplicated surgery; persistent elevation strongly suggests infection 1, 2

Erythrocyte Sedimentation Rate (ESR)

ESR provides complementary information to CRP:

• ESR >27 mm/h combined with CRP >0.93 mg/L and fibrinogen >432 mg/dL achieves 93% sensitivity and 100% specificity when at least 2 of 3 tests are abnormal 2, 4
• ESR remains elevated longer than CRP, useful for monitoring chronic infections 5, 4

Synovial Fluid Analysis: The Gold Standard

Synovial fluid analysis is far more informative than peripheral blood tests 1:

• Synovial WBC count ≥50,000/mm³ has 72.7% sensitivity and 92.3% specificity for infection 3
• Synovial polymorphonuclear cell percentage (PMN%) ≥80% achieves 93.2% sensitivity, superior to absolute WBC count 3
• Synovial alpha-defensin reaches 97% sensitivity and 96% specificity 4

The Bandemia Exception: When WBC Differential Matters

While total WBC count may be normal, examining the differential for bandemia (left shift) can reveal occult infection 1, 6:

• Elevated band count >1500/mm³ has the highest likelihood ratio (14.5) for detecting bacterial infection 1
• Band percentage ≥20% with normal total WBC is associated with 6.2-fold increased odds of positive blood cultures 6
• Percentage of neutrophils >90% has a likelihood ratio of 7.5 for infection 1

Clinical Algorithm for Suspected Orthopaedic Infection

When evaluating suspected orthopaedic infection with normal WBC:

1. Never rely on normal peripheral WBC to exclude infection 1, 2, 4

2. Immediately obtain ESR, CRP, and serum interleukin-6 before starting antibiotics 2, 4

3. Perform joint aspiration for synovial fluid analysis (cell count with differential, culture, Gram stain) before antibiotics 1, 2

4. Withhold antibiotics for at least 2 weeks prior to aspiration when clinically feasible to maximize culture yield 2, 4

5. Check manual differential for bandemia if automated WBC is normal but infection suspected 1, 6

6. Monitor CRP and ESR serially every 2-4 weeks during treatment to assess response 2, 4

Common Pitfalls to Avoid

• Do not use normal WBC count to reassure patients or delay workup for suspected infection 1, 2
• Do not interpret pain as "mechanical" based solely on normal WBC; chronic infections frequently present with pain alone 1
• Do not order imaging before obtaining inflammatory markers and joint aspiration, as this delays definitive diagnosis 2
• Do not start empiric antibiotics before obtaining cultures unless the patient is septic 2, 4