Neutrophil Reactivity Intensity and misclassification of immature granulocytes

Immature granulocyte percentage (IG%) is an important biomarker for infection control. We observed spurious cases where the IG% was dramatically underestimated on the automated Sysmex XN-series hehmatology analyzer compared with manual differential. These cases were associated with high values of "Neutrophil Reactivity Intensity" (NEUT-RI), which should reflect the metabolic activity of the neutrophils.

We conducted a three-stage study to evaluate whether NEUT-RI could be utilized to screen for misclassified IG% results defined as the manual differential estimating a 10 percentage points higher IG% compared with the automated Sysmex differential. First, 124 patient samples were selected for 800-cell manual smear analysis based on their NEUT-RI values and compared with the automatic Sysmex IG% results. Next, 11 098 routine 110-cell manual smear analyses were compared with the corresponding Sysmex IG% results. Finally, during a 19-day period 160 additional patient samples underwent smear based on NEUT-RI values ≥56 fluorescence intensity (FI) to screen for misclassified results beyond our current smear practice.

NEUT-RI ≥56 predicted IG% misclassification with 91% sensitivity and 88% specificity, but primarily when the internal Sysmex flag "Abnormal WBC Scattergram" was present. 90.1% of misclassified results were identified by this flag. Beyond our existing smear rules including this flag, NEUT-RI ≥56 FI had a positive predictive value below 1%.

Both NEUT-RI and the internal Sysmex flag "Abnormal WBC Scattergram" work well to identify cases of IG% misclassification. However, in our setting NEUT-RI ≥56 FI had no meaningful additional predictive capacity to identify misclassifications beyond our current smear rules.