In addition to classical biomarkers of sepsis such as C-reactive protein (CRP), lactic acid, and procalcitonin (PCT), new parameters such as immature granulocytes (IG), which can be obtained from automated hematology analyzers without any additional cost, have been recently proposed as biomarkers for the early detection of sepsis and the evaluation of its severity. Recently launched automatic hematology analyzer Sysmex XN-2000 (Sysmex, Kobe, Japan) can provide 36 routine items as well as 57 items of cell population data (CPD) which reflect detailed status of cells examined. In this study, we evaluated the clinical relevance of CPD items as a biomarker for the diagnosis of sepsis, discrimination of sepsis severity, and prediction of outcome in sepsis patients.
A total of 280 normal controls (NCs) and 130 patients diagnosed as bacterial sepsis were enrolled in this study. The sepsis patients were classified into uncomplicated sepsis (N=29) and complicated sepsis (N=101, defined as severe sepsis and and septic shock) depending on the sepsis severity at the time of sampling. A total of 93 items (36 routine and 53 CPD) were obtained from the Sysmex XN-2000 automatic hematology analyzer and the results were compared between NC and sepsis group at first and between uncomplicated and complicated sepsis group later. In items with significant differences between 2 groups, receiver operating characteristics (ROC) analysis was performed to evaluate discrimination power of the item between 2 groups. In addition, the results of 93 items were compared between survivors and non-survivors after 28 days from the time of sampling, and ROC analysis was also performed to compare the prediction power of the 28-day mortality of each item which showed significant differences between 2 groups.
Among the total 93 items, a total of 21 items showed area under the curve (AUC) more than 0.900 for the discrimination of sepsis patients from NCs. These include routine items such as hematocrit (best cutoff values ≤ 37.2%, AUC 0.964), hemoglobin (≤ 11.7 g/dL AUC 0.961), IG (≥ 0.5%, AUC 0.961), CV of RDW (> 13.7%, AUC 0.951), proportion of lymphocytes (≤ 18.5%, AUC 0.941) and neutrophils (> 72.2%, AUC 0.914). Notably, CPD items NE-SFL (defined as the fluorescent light intensity of the neutrophil area on the WDF scattergram) and NE-WY (defined as the fluorescent light distribution width of the neutrophil area on the WDF scattergram) showed comparative AUC of 0.909 (> 51.6 for NE-SFL) and 0.905 (> 641.0 for NE-WY). However, for the discrimination of sepsis severity, the overall performance of all items was relatively poor and only 3 red blood cell CPD items such as RET-UPP (defined as the count in the upper area of the RET scattergram, ≤ 2.0%, AUC of 0.662), reticulocyte hemoglobin (>33.2 pg, AUC of 0.633), and MacroR (defined as the macrocytic RBC ratio, > 4.60%, AUC of 0.607) and only 1 granulocyte CPD item NE-SFL (> 57.6, AUC of 0.603) showed AUC more than 0.600. The performance of classical sepsis biomarkers was also not satisfactory (AUC of 0.695, 0.543, and 0.537 for lactic acid, CRP, and PCT). For the prediction of 28-day mortality, the overall performance of all items was also not good and only 4 routine items such as CV of RDW (> 15.4%, AUC of 0.766), platelet counts (< 54,000/µL, AUC of 0.677), absolute number of neutrophils (> 12,120/µL, AUC of 0.665), absolute number of reticulocytes (> 2.89 x 106/µL, AUC of 0.650), and 1 CPD item RET-TNC (defined as the count in the TNC area of the RET scattergram, > 125.00, AUC of 0.692) showed AUC of more than 0.650. These results were not superior compared with those from classical sepsis biomarkers (AUC of 0.712, 0.547, and 0.592 for lactic acid, CRP, and PCT).
IG%, the proportion of neutrophils, and 2 granulocytic CPD items (NE-SFL and NE-WY) could discriminate sepsis patients from normal controls when their values increase (which means neutrophil immaturity or activation). Several CPD items showed similar performance compared with lactic acid and slightly better performance than CRP and PCT for the discrimination of sepsis severity and prediction of 28-day mortality. Therefore, it can be speculated that the CPD items of neutrophil immaturity or activation can contribute partly to the discrimination of sepsis patients from NCs, but these items do not discriminate sepsis severity and predict 28-day mortality in sepsis patients as the classical sepsis biomarkers do not.
No relevant conflicts of interest to declare.
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