Age-Dependent Reference Ranges for Automated Assessment of Immature Granulocytes and Clinical Significance in an Outpatient Setting

Abstract

Abstract Context.—New generations of hematology analyzers have made the routine automated quantification of immature granulocytes (IGs) in peripheral blood samples accessible as a powerful clinical parameter. Objective.—The use of IGs has previously been studied mostly in hospitalized patients with sepsis. We investigated the use of IGs in the outpatient setting. Establishment of precise normal outpatient IG reference ranges is a prerequisite for clinically meaningful interpretation of the parameter. Design.—We analyzed a large outpatient population comprising more than 2400 samples to determine age-stratified normal reference ranges for IGs. Results.—Using nonparametric statistical approaches, we show that 1-tailed 95th percentile estimates for relative and absolute IG concentrations up to the age of 10 years are 0.30% and 30.0 µL−1, respectively. For individuals above the age of 10 years, the respective 95th percentile estimates are approximately twice as large at 0.74% and 60.0 µL−1. No differences were seen between male and female reference ranges. Taking nonparametric 90% confidence intervals for each estimate into account, we recommend the following IG upper reference range limits for routine outpatient use: 0.30%/40.0 µL−1 (≤10 years) and 0.90%/70.0 µL−1 (>10 years). Up to the age of 10 years, the most common pathologies associated with elevated IG counts in outpatients were infections, in particular, otitis media, upper and lower respiratory infections, and gastroenteritis. By contrast, above the age of 10 years, the most common causes were hematologic malignancies, drug therapy (glucocorticoids, chemotherapy), severe infections, and pregnancy (young females). Conclusions.—The use of appropriate reference ranges makes IGs a powerful hematologic parameter for outpatient care that is associated with differential diagnoses that are distinctly characteristic of that setting.