What are the causes of a falsely elevated white blood cell (WBC) count?

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Last updated: March 19, 2026 • View editorial policy

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Falsely Elevated White Blood Cell Counts

Falsely elevated WBC counts most commonly result from laboratory interference by nucleated red blood cells, platelet clumps, cryoglobulins, lipemia, incompletely lysed RBCs, and microorganisms (bacteria/yeast), all of which are misidentified as leukocytes by automated analyzers.

Pre-Analytical and Technical Causes

EDTA-Related Issues

  • WBC agglutination in EDTA anticoagulant can paradoxically cause spuriously low counts, but when clumps break apart inconsistently, this may create falsely elevated readings 1

Nucleated Red Blood Cells (NRBCs)

  • NRBCs are the most clinically significant cause of falsely elevated WBC counts because most automated hematology analyzers count them as white blood cells 2
  • NRBCs are normally present in neonates and pregnancy but indicate pathologic hematopoiesis in other adults 2
  • Manual correction of the WBC count is required when NRBCs are present, though cutoff values vary widely between laboratories (commonly 5 or 10 NRBCs per 100 WBCs) 2
  • The corrected WBC formula accounts for the number of NRBCs observed per 100 WBCs during manual differential 2

Platelet Aggregates and Clumps

  • Large platelet aggregates are counted as WBCs by automated analyzers, leading to spuriously elevated counts 1
  • This typically triggers analyzer flags and abnormal WBC differential scattergrams that alert operators 1

Biological Interference

Lipemia

  • Elevated lipids in blood samples interfere with optical measurements, causing falsely elevated WBC counts 1
  • Lipemia affects multiple CBC parameters simultaneously, including hemoglobin and RBC counts 1

Cryoglobulins

  • Cryoglobulins precipitate at room temperature and are counted as cellular elements, artificially increasing WBC counts 1
  • These proteins also cause spurious changes in other measured parameters 1

Incompletely Lysed Red Blood Cells

  • Resistant RBCs that survive the lysis step in automated analyzers are misidentified as WBCs 1
  • This occurs more frequently in certain hemoglobinopathies or when RBC membranes are abnormally resistant 1

Microbiological Interference

Bacteria and Yeast

  • High concentrations of microorganisms (bacteria or yeast) in blood samples significantly elevate WBC counts 3
  • Candida species (C. albicans, C. tropicalis, C. krusei, C. dubliniensis) cause overt WBC elevation at concentrations of 1-5 × 10⁷ CFU/mL across all major analyzer platforms 3
  • C. glabrata and C. parapsilosis require higher concentrations (1-5 × 10⁸ CFU/mL) and show analyzer-specific effects 3
  • The degree of interference varies by both microorganism species and analyzer model (ADVIA, Sysmex, Coulter platforms show different sensitivities) 3

Clinical Recognition and Management

Analyzer Flags and Alerts

  • Modern hematology analyzers generate flags when spurious counts are detected, particularly through abnormal WBC differential scattergrams 1
  • More sophisticated analyzers have better flagging sensitivity; simpler analyzers without differential scattergrams miss many anomalies 1

Key Laboratory Clues

  • Mean corpuscular hemoglobin concentration (MCHC) is the most important calculated index for detecting spurious results, as abnormal MCHC values indicate measurement errors affecting multiple parameters 1
  • When one CBC parameter is spurious, validity of all other parameters should be questioned since multiple measurements are typically affected simultaneously 1

Verification Steps

  • Manual differential with microscopic review is essential when spurious elevation is suspected, particularly to identify NRBCs, microorganisms, or platelet clumps 1, 3
  • Peripheral blood smear review remains the gold standard for confirming true versus false leukocytosis 3

Common Pitfalls

  • Failing to recognize that analyzer flags are critical warnings requiring immediate action, not optional suggestions 1
  • Assuming all elevated WBC counts represent true leukocytosis without checking for technical interference 1
  • Not performing manual correction when NRBCs are present, leading to overestimation of true WBC count 2
  • Ignoring discrepancies between automated counts and clinical presentation 3

References

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