자동혈구분석기 Sysmex XN에서 낮은 값으로 잘못 측정된 백혈구수에 대한 증례: WNR 채널과 WDF 채널 간 차이
A Case of Spuriously Decreased White Blood Cell Count on an Automated Sysmex XN Hematology Analyzer: The Difference Between the WNR and WDF Channels
울산대학교 의과대학 서울아산병원 진단검사의학과
Department of Laboratory Medicine, University of Ulsan College of Medicine and Asan Medical Center, Seoul, KoreaCorrespondence to:
This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
Lab Med Online 2021; 11(3): 191-193
Published July 1, 2021
Copyright © The Korean Society for Laboratory Medicine.
Automated hematology analyzers (HA) are widely used to obtain complete blood cell counts (CBC). CBC are critical for the accurate assessment of patients’ clinical status; thus, the results must be accurate and precise. However, in some cases, spurious CBC can occur, which may require additional action on the part of the clinician to obtain correct results [1, 2]. We report a case of an incorrect white blood cell (WBC) count obtained on a Sysmex XN hematology analyzer (Sysmex Corporation, Kobe, Japan).
A 56-year-old man visited our hospital for follow-up of hepatocellular carcinoma with lung metastases. He had started sorafenib (a molecular targeted multi-kinase inhibitor) 3 months before and nivolumab (a humanized monoclonal antibody to the immune checkpoint receptor programmed death 1 [PD-1]) 2 days before his peripheral blood was drawn for laboratory tests, including CBC. The initial WBC count measured on a Sysmex XN hematology analyzer (Sysmex Corporation) was 0.02×103/μL; the differential count was not available due to the low WBC count. His hemoglobin concentration was 8.5 g/dL and his platelet count was 230×103/μL. After a thorough washout, the repeated analysis showed the same results as initially obtained. The sample was also re-examined in the “low-WBC” mode, which gave a WBC count of 7.16×103/μL. A peripheral blood smear (PBS) was automatically prepared and reviewed according to the laboratory protocol. The WBC count in the PBS was closer to the 7.16×103/μL count obtained in the “low-WBC” mode. WBC aggregation was not observed. A few hypersegmented neutrophils were seen and the monocytes were slightly activated.
Under suspicion of falsely decreased WBC count, the raw data from the hematology analyzer were reviewed. The analyzer displayed the following error message: “Difference between WNR and WDF. Check the results.” The reported WBC count (0.02×103/μL) was obtained from the WBC and nucleated red blood cells (WNR) channel, while the WBC result from the white cell differential (WDF) channel was 7.16×103/μL, the same as the result obtained in ‘low-WBC’ mode, and for which the differential count was available (Table 1). The scattergrams of the two channels were also reviewed (Fig. 1). The scattergram from the WDF channel was more compatible with the PBS findings than the scattergram from the WNR channel. Additional tests were performed to determine the cause of this falsely decreased WBC count. The blood viscosity and neutrophil respiratory burst activity were both within normal limits.
Figure 1. (A) Peripheral blood smear (100×, Wright stain). (B) Scattergrams from the white cell differential (WDF) (left) and white blood cell and nucleated red blood cells (WNR) (right) channels of the Sysmex XN hematology analyzer.
The XN, a fully automated hematology analyzer introduced in 2011, has several new channels compared to the previous model, the Sysmex XE (Sysmex Corporation). Among these, the WNR channel is designed to automatically measure nucleated red blood cells (RBC) at the same time as the CBC is measured. The result from this channel is reported as the default WBC count. The differential WBC count is measured separately through the white cell differential (WDF) channel; however, the WBC count from this channel is not automatically reported. According to the manufacturer, in the WNR channel, samples are treated with a more acidic reagent (pH 2.95–3.05; Lysercell WNR) than that used in the WDF channel (Lysercell WDF). Theoretically, the WBC count from both channels should be the same . However, in the present case, the two channels did not give the same results. Two similar cases have been reported [4, 5].
Zandecki et al.  reviewed factors that can result in inaccurate WBC counts. First, aggregation of polymorphonuclear neutrophils or lymphocytes in blood collected in ethylenediaminetetraacetic acid (EDTA) may result in low WBC counts. Certain anticoagulants, particularly tripotassium (K3)-EDTA, can also cause spurious WBC counts. In our case, no aggregation of leukocytes was seen in the PBS and the sample was collected in dipotassium (K2)-EDTA. It has also been hypothesized that WBCs that are fragile due to cytotoxic agents such as chemotherapy are more prone to lysing, potentially resulting in low WBC counts. However, another report found that chemotherapy did not cause a difference in WBC counts between the WNR and WDF channels . There was also no evidence of WBC lysis in our case. Finally, hyaluronic acid has been reported as a possible cause of WBC aggregation in the presence of the acidic WNR reagent, leading to inaccurate counts . This could be an issue in paraneoplastic syndromes with hypersecretion of hyaluronic acid or hyaluronidase. Unfortunately, we did not measure hyaluronate or hyaluronidase levels to evaluate this possibility.
All clinical laboratories operating automated hematology analyzers should be aware of this phenomenon. When the instrument displays the error message “Difference between WNR and WDF. Check the results”, the raw data from the hematology analyzer and PBS should be carefully reviewed.
- Zandecki M, Genevieve F, Gerard J, Godon A. Spurious counts and spurious results on haematology analysers: a review. Part II: white blood cells, red blood cells, haemoglobin, red cell indices and reticulocytes. Int J Lab Hematol 2007;29:21-41.
- Zandecki M, Genevieve F, Gerard J, Godon A. Spurious counts and spurious results on haematology analysers: a review. Part I: platelets. Int J Lab Hematol 2007;29:4-20.
- Kim H, Hur M, Choi SG, Oh KM, Moon HW, Yun YM. Comparison of white blood cell counts by WNR, WDF, and WPC channels in Sysmex XN hematology analyzer. Int J Lab Hematol 2015;37:869-75.
- Nguyen VT, Gobin D, Li R, Cantinieaux B. Spurious decrease in the WBC count measured by the WNR channel of XN haematology analyser (Sysmex) could be associated with metastatic adenocarcinoma. Int J Lab Hematol 2015;37:e129-32.
- Tantanate C. Spurious white blood cell count from a new automated Sysmex XN hematology analyzer. Int J Lab Hematol 2014;36:e86-7.
- de Jonge R, Brouwer R, Smit M, de Frankrijker-Merkestijn M, Dolhain RJ, Hazes JM, et al. Automated counting of white blood cells in synovial fluid. Rheumatology (Oxford) 2004;43:170-3.