Effect of circadian variation on neutrophil mobilization to the peripheral blood in benign constitutional neutropenia

Highlights

• We evaluated neutrophil circadian variation in benign constitutional neutropenia (BCN).

• BCN patients have a greater neutrophil diurnal increase than controls.

• Neutrophil increment was higher in groups with a lower morning absolute neutrophil count (ANC).

• Afternoon ANC measurement allows many BCN patients to be excluded from neutropenia threshold.

Benign constitutional neutropenia (BCN) is an asymptomatic condition characterized by mild chronic neutropenia in patients with no history of recurrent infections. Most patients are referred for further testing, increasing health care costs. We present an alternative form of assessment of individuals with BCN based on neutrophil circadian variation. The objective of this study was to evaluate whether circadian variations of neutrophil counts would result in neutrophil values higher than neutropenia threshold in individuals with BCN. Absolute neutrophil counts (ANCs) were evaluated in 102 patients with BCN (<1500 cells/μL) and 60 age- and sex-matched controls. Paired blood counts were performed in the early morning and in the early afternoon. We observed a significant difference between morning and afternoon ANC in BCN patients (879 cells/μL, 95% CI 745–1028, p < 0.001), as well as in the controls (619 cells/μL, 95% CI 443–796, p < 0.001). The ANC increase between the two evaluations was significantly greater in BCN patients compared with controls: 83% and 27%, respectively (p < 0.001). The ANC increment was higher in the groups with a lower morning ANC: 105%, 63%, and 27% in the <1000, 1000–1500, and >1500 cells/μL groups, respectively (p < 0.001). Of all BCN patients, 73% presented with >1500 cells/μL in the afternoon and 16% improved from the <1000 cells/μL to the 1000–1500 cells/μL category. In conclusion, neutrophil circadian variation measurement allows many BCN patients to be excluded from the neutropenia threshold. We identified a simple, easy, and feasible way to assess neutrophil reserve in patients with BCN with a potential reduction in costs of the assessment.