From the Guidelines
Elevated neutrophils and lymphocytes require a systematic diagnostic approach, starting with a complete blood count with differential to confirm the elevation and assess other cell lines, as recommended by the American Society of Clinical Oncology 1. The diagnostic workup should include:
- Inflammatory markers (ESR, CRP)
- Comprehensive metabolic panel
- Peripheral blood smear examination
- Consider specific testing based on clinical suspicion, such as:
- Infectious disease workup (blood cultures, viral studies including EBV, CMV, HIV)
- Autoimmune panels (ANA, RF, ANCA)
- Imaging studies such as chest X-ray or CT scan if indicated The elevated neutrophils typically suggest acute bacterial infection, inflammation, or stress response, while increased lymphocytes often point to viral infections, certain chronic infections, or lymphoproliferative disorders, as noted in a study on the management of immune-related adverse events in patients treated with immune checkpoint inhibitor therapy 1. A study on the diagnosis and management of infectious diarrhea also highlights the importance of considering the total white blood cell count and differential in diagnosing bacterial etiologies, and notes that a high total white blood cell count and neutrophil count often occur in patients with STEC O157 infections who subsequently develop HUS 1. A bone marrow examination may be necessary if leukemia or other hematologic malignancies are suspected, as recommended by the Society for Immunotherapy of Cancer 1. Management depends on identifying the underlying cause rather than treating the laboratory abnormality itself, and follow-up testing should be scheduled to monitor the response to any interventions and to ensure resolution of the abnormalities.
From the Research
Elevated Neutrophils and Lymphocyte Work Up
- An elevated white blood cell count, including neutrophils and lymphocytes, can have various etiologies, including malignant and nonmalignant causes 2.
- In patients with hematologic malignancies, inflammatory markers such as neutrophil-lymphocyte ratio (NLR), platelet-lymphocyte ratio (PLR), and derived neutrophil-lymphocyte ratio (dNLR) are significantly increased compared to age-matched controls 3.
- The dNLR has been shown to have a high area under the curve (AUC) score for diagnosing hematologic malignancies, with a value of 0.810 and a 95% CI of 0.646-0.975 3.
- Combining multiple inflammatory markers, including NLR, PLR, PMR, HLR, SII, and dNLR, can result in an even higher AUC score of 0.923 with a 95% CI of 0.778-1.000 3.
- A repeat complete blood count with peripheral smear and leukocyte differential can provide helpful information in evaluating patients with leukocytosis, including the types and maturity of white blood cells and the presence of toxic granulations 2.
- Symptoms suggestive of a hematologic malignancy, such as fever, weight loss, bruising, or fatigue, should prompt further evaluation and potential referral to a hematologist/oncologist 2.