At a Glance
Neutrophilia is defined as an absolute neutrophil count (ANC) greater than 2SD above the mean for the patient population. Typically, this represents a neutrophil count greater than 7700/microliter (µL).
Note that a finding of neutrophilia should not be based on a differential count reported in percentages. Depending on the total white cell count (WBC) an elevation in the percentage of neutrophils may reflect either true neutrophilia (high WBC) or lymphopenia (normal or low WBC). Therefore, the diagnosis of neutrophilia should be based on an absolute neutrophil count either provided directly by the performing laboratory or calculated (ANC = WBC x % neutrophils x 100).
What Tests Should I Request to Confirm My Clinical Dx? In addition, what follow-up tests might be useful?
In a patient without an obvious cause for neutrophilia (e.g., signs or symptoms of infection or inflammation), it is most appropriate to simply repeat a complete blood count (CBC) on a new sample to confirm that neutrophilia is truly present. Although uncommon, sample mislabeling, laboratory error, spurious neutrophilia, and/or patient stress may all result in an erroneous or transient neutrophilia that may simply disappear on repeat testing.
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If neutrophilia is present on repeat testing, the next step is to thoroughly review the remainder of the CBC for other abnormalities and ask the laboratory to review a well-made peripheral smear for red cell, white cell, and platelet morphology.
Review the CBC; in particular, look for any of the following:
leukocytosis
anemia
polycythemia
thrombocytopenia
thrombocytosis
high or low MCV
Review the peripheral smear for:
General assessment (i.e., evidence of red cell or platelet clumping that may cause spurious leukocytosis and neutrophilia)
Leukocyte morphology (i.e., presence of immature granulocytes, and monocytes or blasts (leukemoid reaction, leukoerythroblastosis, leukemia, myloproliferastive disorder); left shift, toxic granulation, Dohle bodies, and cytoplasmic vacuoles (acute inflammation or infection); hypersegmantation (early recovery of vitamin deficiency, myelodysplasia); Pelger-Huet or pseudo-Pelger-Huet cells (myelodysplasia, Pelger-Huet disorder); and intracellular organisms (severe sepsis, Ehrlichosis, disseminated fungal infection)
Red cell morphology (i.e., nucleated red cells (marrow infiltration, leukoerythroblastosis, marrow recovery); dysplastic forms (myelodysplasia); intracellular organisms (Malaria sp., Babesia sp.); spherocytes (microangiopathic processes, DIC, burns, immune hemolysis); schistocytes (TTP, HUS, DIC, endocarditis, other microangiopathic processes); sickle cells (HbSS as a cause of asplenia); and marked polychromasia (marrow recovery)
Platelet morphology (i.e., large platelets (marrow recovery) and abnormal platelet shape or granulation (myelodysplasia))
In an asymptomatic patient with mild neutrophilia and no associated CBC or peripheral smear abnormalities, the laboratory evaluation could justifiably stop at this point with a plan to repeat testing if symptoms develop and/or in several weeks to determine if the neutrophilia is persistent. If neutrophilia persists, assessment of the patient for hematologic or genetic disorders may be warranted.
Are There Any Factors That Might Affect the Lab Results? In particular, does your patient take any medications – OTC drugs or Herbals – that might affect the lab results?
Spurious neutrophilia may be due to the presence of either platelet or red cell masses that the CBC analyzer may interpret as leukocytes/neutrophils. A review of the peripheral smear and/or repeating the CBC on a fresh sample may demonstrate this as the cause of the apparent neutrophilia.
Patient stress (e.g., emotional distress, depression, exercise, pain, etc.) may cause neutrophil demargination and a transient mild neutrophilia. Repeating the CBC when the patient is not under stress may demonstrate a resolution of the elevated neutrophil count.
Several medications, as well as smoking, are known to cause neutrophilia and/or leukocytosis. Implicated medications include, but are not limited to, corticosteroids, lithium, epinephrine, and granulocyte colony stimulating factor (G-CSF) or granylocyte/macrophage colony stimulating factor (GM-CSF). If the patient has recently begun any new medications, consideration should be given to discontinuing or lowering the dosage to see if the neutrophilia resolves.
Asplenic patients, either due to trauma, surgery, or autosplenectomy (e.g., Sickle Cell disease), have mildly elevated neutrophil and leukocyte counts due to lack of sequestration of these cells within the spleen.
What Lab Results Are Absolutely Confirmatory?
A repeat CBC performed on a separate sample when the patient is not stressed, is off any potential causative medications (if possible), and in which there is no evidence of spurious neutrophilia confirms the diagnosis.
Additional Issues of Clinical Importance
Although the most common causes of neutrophilia are inflammation and/or infection, it may also be associated with several inherited or neoplastic conditions that would generally require specialist referral to assess.
Patients with neutrophilia associated with other CBC abnormalities and/or peripheral smear findings suggesting a clonal disorder (e.g., immature leukocytes, blasts, dysplastic leukocytes, or red cells or platelets) should be referred to a Hematologist for complete hematologic assessment. Such an assessment may include bone marrow examination and staining, flow cytometry, and cytogenetic and/or molecular genetic testing, as well as imaging studies.
Patients with persistent neutrophilia, without evidence for inflammation, infection, or neoplasia, may have a genetic basis for their elevated neutrophil count. Although most inherited conditions associated with neutrophilia are benign, some are associated with clinical symptoms and signs, disease risks, and/or decreased lifespan. Therefore, such patients may benefit from a thorough genetic evaluation and counselling.
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