Evaluation of neutrophilia

Neutrophilia is defined as an elevated circulating neutrophil count (>7700/microliter) in adults with a normal total WBC count of <11,000/microliter.[1]Hoffman R, Furie B, McGlave P, et al. Hematology basic principles and practice. Philadelphia, PA: Elsevier Churchill Livingston; 2009.The terms hyperleukocytosis and leukemoid reaction are reserved for total leukocyte counts of >50,000/microliter, with leukemoid reaction defined as having a nonmalignant etiology. An elevated total WBC count (>11,000/microliter) and an absolute neutrophil count >7700/microliter is defined as a neutrophilic leukocytosis.[1]Hoffman R, Furie B, McGlave P, et al. Hematology basic principles and practice. Philadelphia, PA: Elsevier Churchill Livingston; 2009. The absolute neutrophil count can be estimated by multiplying the total WBC count by the percentage of polymorphonuclear cells and band forms (immature neutrophils have a band-shaped nucleus). The terms granulocytosis and neutrophilia are often used interchangeably, although granulocytosis also includes elevations in eosinophils and basophils.

Neutrophilia results from an increased production of neutrophils, demargination (process of neutrophils entering the peripheral circulation from areas of intravascular marginated polymorphonuclear cell pools), or decreased egress (outward migration) of neutrophils from peripheral circulation to the tissues.[Figure caption and citation for the preceding image starts]: NeutrophiliaFrom the collection of T. George, MD [Citation ends].

Epidemiology

Generalizing which patients are most at risk for neutrophilia is limited, as multiple factors contribute to the development of neutrophilia. Evaluation of the opposite condition, neutropenia (an absolute neutrophil count <1500/microliter), has demonstrated reproducible ethnic differences.[2]Hsieh MM, Everhart JE, Byrd-Holt DD, et al. Prevalence of neutropenia in the U.S. population: age, sex, smoking status, and ethnic differences. Ann Intern Med. 2007;146:486-492. http://annals.org/article.aspx?articleid=733880 http://www.ncbi.nlm.nih.gov/pubmed/17404350?tool=bestpractice.com Relative to white people, black people have a lower total WBC count (mean difference 890/microliter) and lower neutrophil count (mean difference 830/microliter). In contrast, Hispanic people have a higher leukocyte count (mean difference 160/microliter) and higher neutrophil count (mean difference 110/microliter) relative to white people. Lifestyle factors also influence the risk of neutrophilia, including exercise levels, stress, and smoking status.

Pathophysiology

The peripheral circulation of neutrophils, which is included in the total leukocyte count, consists mostly of mature neutrophils in transit from the bone marrow to peripheral tissues. This process is short, lasting about 3 to 6 hours, and depends on signaling through the chemokine receptor CXCR4 on the surface of neutrophils. Only 5% of the total number of neutrophils is present in the circulation at any one time, as the neutrophil lifespan includes 9 days within the bone marrow, and 1 to 4 days in peripheral tissues, with only 3 to 6 hours spent in the circulation.

Bone marrow production of cells within the myeloid lineage is stimulated by interleukin 3 and granulocyte macrophage colony-stimulating factor. Granulocyte colony-stimulating factor, however, is responsible for catalyzing differentiation of early myeloid cells into mature neutrophils. Multiple signals induce neutrophil migration to the peripheral circulation from the marrow, including corticosteroids, endotoxins, complement-derived leukocyte-mobilizing factor, C5a chemoattractant, TNF-alpha, and androgens. When triggered, release of neutrophils from bone marrow storage triples circulating neutrophils within 4 hours. In addition to neutrophils contained within the bone marrow, circulation, and peripheral tissues, a moderate population adheres to the vascular endothelium and enters the circulation on demargination. Release of catecholamines, including epinephrine, results in almost immediate demargination and subsequent doubling of the peripheral neutrophil count.