Revision in Reference Ranges of Peripheral Total Leukocyte Count and Differential Leukocyte Percentages Based on a Normal Serum C-Reactive Protein Level

A higher total leukocyte count is a predictor of all-cause mortality and cardiovascular morbidity. The currently used reference range for peripheral total leukocyte count is wide (4.5–11.0 × 109/L) and is associated with a low sensitivity in identifying non-infectious chronic diseases. We attempt to revise it based on a normal serum C-reactive protein (CRP) level. Methods: Study subjects were participants in a health check program at our hospital between 2000 and 2002. Those whose leukocyte analysis had been checked with the Sysmex Cell Counter NE-9000 were enrolled. Results: Significantly positive relationships between CRP level and total leukocyte count, neutrophil percentage, and monocyte percentage were found in all subjects (n = 14,114; p< 0.0001). In contrast, CRP level had a significantly inverse correlation with lymphocyte percentage (p < 0.0001). A proposed new reference range for total leukocyte count was estimated based on the data in the normal CRP level group (CRP < 0.1 mg/dL; n = 4839). To rest on the essence of statistics that the range of [mean ± 2 standard deviations] contains approximately the middle 95% of observations in a sampled population, a new reference range for total leukocyte count was accordingly estimated to be 3.11–8.83 × 109/L. Conclusion: In view of the abundant evidence showing that a higher peripheral total leukocyte count is harmful to health, a down-correction of its upper reference range from the currently used 11.0 × 109/L to the proposed 8.83 × 109/L, based on a normal CRP level, should allow more abnormal health conditions to be identified and promote the usefulness of peripheral leukocyte analysis