Can Influenza Cause Leukopenia, Neutropenia, and Monocytosis?
Yes, influenza commonly causes low white blood cell counts (leukopenia) with low neutrophils (neutropenia), and can be associated with elevated monocytes (monocytosis) as part of the inflammatory response to viral infection.
Expected Hematologic Findings in Influenza
Leukopenia and Lymphopenia
- Low WBC is common in influenza A in children, occurring in 27% of cases (WBC <4.0) and 24% of cases (WBC <5.0) 1
- Lymphopenia is particularly characteristic, found in 41% of cases (lymphocytes <1.5) and 40% of cases (lymphocytes <1.0) 1
- In contrast, elevated WBC (>15) is found in only 8-12% of influenza cases, making leukocytosis uncommon 1
- Influenza A is specifically associated with leukopenia, though isolated thrombocytopenia, anemia, or pancytopenia can occur transiently 2
Neutrophil Changes
- Neutrophil counts are typically reduced in influenza infection 1
- However, neutrophil surface receptor expressions (CD11b and CD66b) are paradoxically increased during influenza, suggesting enhanced recruitment to infected areas despite lower absolute counts 3
- Phagocyte receptor expression on neutrophils (CD64, CD32, CD35, CD16) is impaired in influenza, which may contribute to increased susceptibility to secondary bacterial infections 3
Monocyte Response
- Monocyte expressions of adhesion molecules (CD11b and CD18) are elevated in influenza compared to bacterial infection and healthy controls 3
- This up-regulation of monocyte adhesion molecules suggests increased recruitment to infected areas as part of the inflammatory response 3
- Monocyte phagocyte receptor expression is increased in all infected groups, contrasting with the impaired neutrophil receptor expression 3
Severe Influenza Patterns
H5N1 Avian Influenza
- In severe H5N1 cases from Vietnam, 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
- Survivors of H5N1 had higher WBC (mean 12.44) and lymphocyte counts (mean 3.11), suggesting that profound leukopenia predicts worse outcomes 1
Neutrophil-Dominated Severe Disease
- Patients with severe influenza display excessive neutrophil activation, including neutrophil extracellular trap formation, neutrophil-inflammation, and delayed apoptosis 4
- Excessive neutrophil activation correlates with worsening oxygenation impairment and predicts fatal outcome (AUROC 0.817-0.898) 4
Clinical Recommendations for Laboratory Testing
When to Order CBC
- A full blood count with differential should be done in all severely ill children with influenza 1
- The British Infection Society and British Thoracic Society recommend CBC for all patients admitted to hospital with influenza-like illness 5
- Additional tests should include urea, creatinine, electrolytes, liver enzymes, and blood culture in severely ill patients 1, 5
Interpreting Results
- C-Reactive Protein (CRP) is unhelpful in influenza, with values <10 in 55% and <20 in 72% of cases 1
- Thrombocytopenia (<100) is found in 5-7% of influenza A cases 1
- Liver transaminases are raised in 27% of influenza A patients 1
Important Clinical Caveats
Distinguishing Viral from Bacterial Superinfection
- Secondary bacterial pneumonia typically develops 4-5 days from onset of initial influenza symptoms 1, 6
- The impaired phagocyte receptor expression on neutrophils during influenza may contribute to increased susceptibility to bacterial superinfection, particularly with encapsulated bacteria like pneumococci 3
- Leukocytosis with left shift may indicate secondary bacterial pneumonia rather than pure viral infection 5
Transient Nature of Cytopenias
- Cytopenias associated with influenza are typically transient and improve as viral symptoms resolve 2
- All patients with influenza-associated cytopenias improve spontaneously without specific intervention 2