Typical Laboratory Abnormalities in Infectious Mononucleosis
Infectious mononucleosis characteristically presents with lymphocytosis where lymphocytes comprise at least 50% of the white blood cell differential, with atypical lymphocytes constituting more than 10% of the total lymphocyte count. 1
Hematologic Findings
White Blood Cell Abnormalities
- Peripheral blood leukocytosis occurs in most patients, though only 46.2% demonstrate frank leukocytosis in some series 1, 2
- Lymphocytes make up at least 50% of the white blood cell differential count 1
- Atypical lymphocytes exceed 10% of the total lymphocyte count, with 89.2% of confirmed cases showing atypical lymphocytosis 1, 2
- The atypical lymphocytes are predominantly activated CD8+ T cells, with marked increases in CD8+/CD57-, CD8+/CD95+, and CD8+/CD28+ subsets 3
Lymphocyte Subset Changes
- Absolute CD8+ T cells are significantly elevated, representing the primary cellular response to EBV infection 3
- Natural killer (NK) cells (CD3-/CD16/56+) show moderate increases 3
- Gamma-delta T cells (CD3+/gammadelta+) are characteristically increased in EBV-positive cases compared to other causes of atypical lymphocytosis 3
- CD4+ T cell and CD19+ B cell absolute counts remain unchanged, which helps distinguish infectious mononucleosis from other lymphoproliferative disorders 3
Hepatic Abnormalities
Liver Enzyme Elevations
- Elevated liver enzymes occur in 57.9% of laboratory-confirmed cases 2
- Markedly elevated transaminases (>10x normal) should be considered as EBV-associated acute hepatitis 4
- Aspartate aminotransferase (AST), alanine aminotransferase (ALT), and lactate dehydrogenase (LDH) are commonly elevated 5
Bilirubin Abnormalities
- Hyperbilirubinemia occurs in 14.9% of cases, which is relatively high compared to historical reports 2
Serologic Markers
Heterophile Antibodies
- The heterophile antibody becomes detectable between days 6-10 after symptom onset and peaks during weeks 2-3 of illness 6
- False-negative results occur in approximately 10% of patients, particularly in children younger than 10 years 6
EBV-Specific Antibodies
- VCA IgM antibodies indicate acute/recent infection and are present in primary infection 6, 4
- VCA IgG antibodies develop rapidly in acute infection 6
- EBNA antibodies are absent in acute infection and develop 1-2 months after primary infection, making their absence critical for confirming recent infection 6, 4
Common Pitfalls in Laboratory Interpretation
- Do not assume leukocytosis is always present - nearly half of confirmed cases may have normal white blood cell counts 2
- The classic triad of fever, sore throat, and lymphadenopathy has low sensitivity (68.2%) and specificity (41.9%) for EBV infection, so laboratory confirmation is essential 2
- Atypical and typical presentations of infectious mononucleosis show no significant differences in peripheral white blood cell counts, lymphocyte percentages, or liver enzyme levels, meaning atypical cases can only be identified through maintaining high clinical suspicion 5
- In children under 10 years, proceed directly to EBV-specific antibody testing rather than relying on heterophile tests due to higher false-negative rates 6, 4