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International Journal of Laboratory Hematology

The Official journal of the International Society for Laboratory Hematology

ORIGINAL ARTICLE

INTERNATIONAL JOURNAL OF LABORATO RY HEMATO LOGY

Optimization of laboratory workflow in clinical hematology laboratory with reduced manual slide review: comparison between Sysmex XE-2100 and ABX Pentra DX120
M. HUR*, J.-H. CHO*, H. KIM*, M.-H. HONG*, H.-W. MOON*, Y.-M. YUN*, J. Q. KIM †

*Department of Laboratory Medicine, Konkuk University School of Medicine, Seoul, Korea † Konkuk University, Seoul, Korea Correspondence: Mina Hur, Department of Laboratory Medicine, Konkuk University School of Medicine, Konkuk University Hospital, 4-12, Hwayang-dong, Kwangjin-gu, Seoul 143-729, Korea. Tel.: +82 2 2030 5581; Fax: +82 2636 6764; E-mail: dearmina@hanmail.net This work was supported by Konkuk University in 2010.
doi:10.1111/j.1751-553X.2011.01306.x

SUMMARY

Received 24 September 2010; accepted for publication 21 December 2010 Keywords Slide, review, Sysmex XE-2100, ABX Pentra DX120, hematology

Introduction: The validation of automated hematology analyzer results by manual slide review (MSR) is currently an inevitable work process in clinical hematology laboratories. The laboratory workload would be optimized if the requirement for MSR could be reduced without compromising patient care. We investigated whether slide-making rates would be different between two hematology analyzers, which were paired with their own automated slide makers/stainers: Sysmex XE-2100 with SP-1000i (Sysmex, Kobe, Japan) and ABX Pentra DX120 with SPS evolution (ABX-Horiba, Montpellier, France). Methods: A total of 943 samples were run in parallel on the Sysmex XE-2100 and ABX Pentra DX120. Reflex slides were automatically made in each analyzer according to its own criteria, which reflected the criteria of MSR in our laboratory. The slide-making rates were compared, and the results were further confirmed using the criteria of MSR. Results: The slide-making rates in Sysmex XE-2100, ABX Pentra DX120, and manual review were 22.5% (212/943), 15.91% (150/ 943), and 11.5% (108/943), respectively. In 774 (82.1%) samples, the three methods showed concordant results, and all made slides in 82 samples. Using the manual method as a standard, the sensitivity and specificity were 86.1% and 85.8% in Sysmex XE-2100 and 89.8% and 93.7% in ABX Pentra DX120. Conclusion: Our data show that the slide-making rates are variable in different hematology analyzers. It also implies that although MSR cannot be fully substituted by modern hematology analyzers, it can be effectively reduced to optimize laboratory workload.

INTRODUCTION
The complete blood count (CBC) with leukocyte differential counts (LDC) is one of the most frequently
Ó 2011 Blackwell Publishing Ltd, Int. Jnl. Lab. Hem.

requested tests in clinical laboratories. Technical evolutions in automated hematology analyzers have improved the analytic performance greatly and have broadened the range of information provided (Buttarello
1

Accordingly. the implementation of these criteria in the different hematology analyzers could vary according to the characteristics of each analyzer. Barnes et al. France).1. or immature granulocytes. the rates of slide preparation and review might be highly affected. we needed another process to identify samples from the hematology department. such as reticulocyte indices. or certain components of LDC are less satisfactory (Buttarello. their sensitivities and specificities were analyzed using MedCalc Software (version 11. 2002. which were programmed to reflect the criteria of MSR in our laboratory. Int. the criteria in each analyzer were developed not to miss any pathological samples. and the workflow of slide review was developed according to the use of this analyzer and its automated slide makers/stainer. MedCalc Software.. Thomas et al. and the results were further confirmed with those of manual review. have not yet been fully established or standardized (Buttarello et al. the SP-1000i (Figure 2).2 M. Ó 2011 Blackwell Publishing Ltd. the red blood cell count (RBC). the sensitivity and specificity of each analyzer were obtained. Automated slide makers and strainers. 2004. Each laboratory has its own decision-making criteria or rules for the validation of quantitative abnormalities or qualitative alterations that are highlighted (flagged) and which trigger slide preparations and reviews as reflex tests (Lantis et al. Jnl. Consequently. 2004. The rules for slide making in the Sysmex XE2100 are listed in Table 1. 2005). Segal et al. hemoglobin concentration (Hb). reticulated platelets. Sandhaus & Meyer. 2009). Hem. MATERIALS AND METHODS A total of 943 patient samples were randomly selected from the daily routine workload of our hematology laboratory and were run in parallel on the Sysmex XE-2100 and ABX Pentra DX120.. immature reticulocyte fraction. For such samples. One of the criteria for slide review was to review all the samples from the hematology department regardless of CBC abnormalities. are widely used in high-volume hematology laboratories (Simson. Although each laboratory has criteria that trigger reflex slides. while the results for reticulocytes. Laboratory work processes would be optimized if the number of MSR could be reduced without compromising patient care. To increase the clinical sensitivity. Despite the high-quality performances and expanded capabilities of automated analyzers... Reflex slides were automatically prepared by each analyzer according to its own criteria. Using the manual review as a standard. Kobe. The slide-making rates were compared between the two analyzers. .. 2003. The main differences in the rules between the Sysmex XE-2100 and ABX Pentra DX120 were that department information and delta check could be included in the criteria for the ABX Pentra DX120. Briggs et al. 2006). Gascon-Lema & Brown. Montpellier.2. Among the traditional CBC parameters. In such situations. together with their hematology analyzers. white blood cell count (WBC).. The decision-making criteria for MSR in our laboratory are presented in Figure 1. To compare the diagnostic performances of Sysmex XE-2100 and ABX Pentra DX120. the manual examination of blood smears still plays an important role in hematology laboratories. Japan) and ABX Pentra DX120 with SPS evolution (ABX-Horiba. and the workflow of the rules in ABX Pentra DX120 is summarized in Figure 3. 2005). slide preparation and staining were performed manually. HUR ET AL. 2002. The statistical differences in their sensitivities and specificities were obtained with chi-square test. Belgium). This study investigated whether the slidemaking rates were different between two hematology analyzers that were paired with their own automated slide makers/stainers: Sysmex XE-2100 with SP-1000i (Sysmex. The clinical applications and analytical function of the newly introduced parameters. for which slides were not prepared. 2008). and mean cell volume generally show excellent analytical function. One expert senior technologist checked all the CBC data and reflex slides that were automatically prepared from each analyzer and slide maker/stainer combination to choose the slides to be reviewed. in addition to the main workflow of slide preparation through SP-1000i.. reflex slides are automatically prepared after the generation of abnormal CBC data. Mariakerke. The Sysmex XE-2100 is used as the main hematology analyzer in our laboratory. REDUCED SLIDE REVIEW IN HEMATOLOGY LABORATORY & Plebani. 2005). with no manual intervention by experienced laboratory staff. Lab. platelet counts. The laboratory workload and efficiency of generating the final CBC report are widely affected by the number of manual slide review (MSR) performed and are variable between laboratories (Novis et al.

22.91% (150/943).M.5% (108/943). and manual review are presented in Table 2. The slide-making rates in Sysmex XE-2100.1%) samples: all positive in 82 samples and all negative in 692 samples. Int. Workflow of slide review with Sysmex XE-2100 and SP-1000i. Hem. Discrepant results were observed in 169 samples. Lab. HUR ET AL. RESULTS The comparison data of slide preparation by Sysmex XE-2100. REDUCED SLIDE REVIEW IN HEMATOLOGY LABORATORY 3 Figure 1. ABX Pentra DX120. respectively. and MSR were Ó 2011 Blackwell Publishing Ltd. No case showed a positive result by manual review but . All the three methods showed concordant results in 774 (82.5% (212/943). and 11. 15. Figure 2. Jnl. ABX Pentra DX120. The decision-making criteria for manual slide review.

Compared with manual procedures.8. except for one sample with 3% basophils (sample 8). slide flag was the most frequent cause followed by delta check and department.8%). In ABX Pentra DX120. The causes of false-positive and false-negative results were analyzed (Table 4).5–94. with a difference of 3. The quantitative values or flags in 11 samples with false-negative results by ABX Pentra DX120 are presented in Table 5.2–10. respectively (Table 3). In the 119 samples with false-positive results by Sysmex XE-2100.0%) in Sysmex XE-2100 and 89. there may be a discrepancy between the prepared slides and reviewed slides. Jnl.8% (95% CI. the sensitivity and specificity were 86.4 M. platelet count. To increase the clinical sensitivity. red blood cell count.1% (95% confidence interval (CI).0% (95% CI.2%) and monocytosis with large immature cells (35. the rates of MSR varied considerably among participants (26. negative results by both Sysmex XE-2100 and ABX Pentra DX120.0%) and 85. P = 0.7%) of the total falsepositive causes. Lab. there were discrepant results between the Sysmex XE-2100 and ABX Pentra DX120 in 26 samples with positive MSR results: 15 were Sysmex negative and Pentra positive and the other 11 were Sysmex positive and Pentra negative. 2006). slide flag and/or delta check comprised three-quarters (75. the causes were department (n = 11) and absence of result (n = 4) in Sysmex XE-2100.0165) for sensitivity and 8. and 50. However. the use of automated slide makers and stainers has increased in large-sized clinical laboratories. 5. Int. not all the automatically prepared slides are reviewed manually. 82. Considering the general policy of laboratories not to miss Ó 2011 Blackwell Publishing Ltd.7% (95% CI. RBC. Gascon-Lema & Brown. They are used in combination with their multiparameter hematology analyzers.8%) and 93.5% Lymphocytopenia/lymphocytosis: <10% or >70% Monocytosis: monocytes > 15. P < 0.5% Eosinophilia: eosinophils > 20% Basophilia: basophils > 2% Nucleated RBCs > 2/100 WBCs Thrombocytopenia/thrombocytosis: PLT < 100 · 109/l or PLT > 600 · 109/l Flags PLT clumps or abnormal distribution Fragments Blasts Immature granulocytes Left shift Atypical lymphocytes Abnormal lymphocytes/lymphoblasts WBC. white blood cell count. PLT.. and their performances are reported to be comparable to well-prepared manual processes (Simson. 91. 83.8–95. . This would be more conspicuous especially when a hospital has a large pool of hemato-oncological patients. HUR ET AL. That study showed that the rates of MSR were directly related to the efficiency in generating CBC results.9% in the 10th percentile. and these threshold limits also varied widely among participants.2%) in ABX Pentra DX120. and absence of flag (n = 11) in ABX Pentra DX120. Hem.0 · 109/l or WBC > 20 · 109/l Neutropenia/neutrophilia: neutrophils < 30% or neutrophils > 85. most laboratories tend to develop less strict criteria so as not to miss potentially important abnormalities.71.0001) for specificity (chi-square test). On the other hand. these did not correspond to our criteria for the manual confirmation. REDUCED SLIDE REVIEW IN HEMATOLOGY LABORATORY Table 1.1–92. the two causes of false-positive results were slide flag (64. the introduction of automated slide makers and stainers has significantly reduced the workload of slide preparation as well as the turn-around-time of the final CBC report. If slide-making rules of the instrument do not perfectly match the slide-review criteria of the laboratory. DISCUSSION The manual examination of blood smears is time-consuming and expensive and may not be always necessary. 2009). However. 0.2–88. The rules for slide making in Sysmex XE-2100 Quantitative abnormalities Leukocytopenia/leukocytosis: WBC < 2. The Sysmex XE-2100 also showed flags and/or quantitative abnormalities that triggered MSR in these 11 samples. According to the College of American Pathologists’ Q-Probes Study with 263 participating institutions.8% (95% CI. Significant differences in the specificity and specificity of the analyzers were observed. Most of the MSR were triggered by hematology analyzer flags.7% in the median. 78.0% in the 90th percentile institutions) and were elevated with increased numbers of hospital beds (Novis et al.7% (95% CI. Recently. 9. Regarding false-negative results. Using MSR as a reference method.69– 6.

4) (9. no study has focused on this practical issue in routine hematology laboratory so far. This study investigated whether the slide-making rates would be different between two hematology analyzers when paired with their own automated slide . Int. Lab. construction of the rules to reflect the laboratories’ own criteria may be variable in Ó 2011 Blackwell Publishing Ltd. Pentra multilink data management system. the presence of these unnecessarily prepared slides might be regarded as inevitable. each hematology analyzer. Hem.M. HUR ET AL. ABX Pentra DX120. and consequently. Slide preparation by Sysmex XE-2100. SPS evolution.1) Table 3. REDUCED SLIDE REVIEW IN HEMATOLOGY LABORATORY 5 Figure 3.2) (1.6) (0) (73. and manual review Sysmex XE-2100 Positive Positive Negative Negative Negative Positive Negative Positive ABX Pentra DX120 Positive Negative Positive Negative Negative Negative Positive Positive Manual review Positive Positive Positive Positive Negative Negative Negative Negative Number (%) 82 11 15 0 692 90 24 29 (8. However. the gap between the prepared and reviewed slides may be different. ABX Pentra DX120. Jnl. To the best of our knowledge. PML. Workflow of the rules for slide making in Pentra DX120. ABX Pentra DX120.5) (2. any possible pathologic samples.5) (3. and manual review Sysmex XE-2100 Positive Manual review Positive 93 (n = 108) Negative 119 (n = 835) Negative ABX Pentra DX120 Positive Negative 15 716 97 53 11 782 Positive means the slide preparation. Table 2.7) (1. PDX. and negative vice versa. SPS. Comparison of the results between Sysmex XE-2100.

Aty L: 1 N: 78. 35. 100%) Department (n = 11. 17.8. atypical lymphocytes. L: 17.4.7 M: 12. L-Blasts. L: 12.8. Mm.3%) No result (n = 4. Abn L. platelet aggregates. Nb: 1. Aty L: 2.7%) ABX Pentra DX120 Total (n = 53. Lic: 0. L. PED. or immature granulocytes and/or quantitative abnormalities by Sysmex XE-2100 (Table 5). which could not be included in the rules for Sysmex XE-2100 (Table 4). large immature cells. nRBC. eosinophils. HUR ET AL. M: 4. monocytosis. 38. Nb: 4. B: 1 8 9 10 11 IM PED IM IM Blasts Neutropenia.6%) Slide flag and delta check (n = 10. abnormal lymphocytes. and in the routine practice of our laboratory. and the main causes of difference were attributable to ‘delta check’ and ‘department’. E: 2. B: 2. N. 26. Nb: 2. L: 43. E: 1. Jnl. 28. M: 6 N: 65. internal medicine. Nb: 2. M: 4. Lic.7%) Delta check (n = 34. Aty L: 1 N: 79. ‘Department’ was also the main cause of false-negative results in Sysmex XE-2100. E:3. E: 2. 8. E: 3. 64. . and the Ó 2011 Blackwell Publishing Ltd. In contrast.2 M:13.0 E: 16. Our data showed that the sensitivity and specificity of slide preparation were different between these two systems and that the performance of ABX Pentra DX120 with SPS evolution was superior to that of Sysmex XE-2100 with SP-1000i (Table 3).8%) False-negative Total (n = 11. According to our decision-making criteria for slide review. they mostly showed flags of blasts. 100%) Slide flag (n = 34.2%) Mono + Lic (n = 19. B: 1. Nb: 4. L:16. lymphocytes.0 Lic: 2. L: 25. E: 4. Nb: 2. REDUCED SLIDE REVIEW IN HEMATOLOGY LABORATORY Table 4.2) Lic: 2. Aty L: 1. 73. Abn L/L-Blasts Aty L Aty L N: 46. M: 9. L: 64. Int. Table 5. 100%) Slide flag (n = 46. department. Quantitative values or flags in samples with false-negative results by ABX Pentra DX120 Quantitative values (%) or flags Dep 1 2 3 4 5 6 7 IM IM IM IM IM IM IM ABX Pentra DX120 Lic: 1. L: 10. Aty L: 1 N: 61.4. Aty L: 3 Dep. MSR was triggered by the results of Sysmex XE-2100. neutrophils. Lic: 0. 100%) No flag (n = 11. Nb. IM. Lic: 0. 100%) Mono + Lic. L: 22.4) Lic: 0.2. atypical lymphocytes. metamyelocytes.6. makers/stainers: Sysmex XE-2100 with SP-1000i and ABX Pentra DX120 with SPS evolution. Blasts Abn L/L-Blasts Aty L Immature Granulocytes Abn L/L-Blasts Basophilia Manual differential count (%) N: 67.7%) Total (n = 15. this was one of the main causes of extra workload. M:6. L: 25. band-form neutrophils.9 Neutropenia (M: 10. M: 13.6%) Department (n = 21. Eleven samples showed false-negative results by ABX Pentra DX120 with no flags. M: 11. In particular. M: 8. Aty L: 1. My. Aty L: 1.6 M. nucleated RBCs. Aty L: 0. L: 39. monocytes. L: 8.4 Sysmex XE-2100 Abn L/L-Blasts Eosinophilia. B: 2. Aty L: 1. M: 7. B: 1 N: 65.9 No flags Lic: 1.5 nRBC. B: 3 N: 15. Aty L. myelocytes.4%) Department and delta check (n = 8. pediatrics. Nb: 2. B: 1.0.6. M. M: 5. basophils. M: 6. (M: 11. Mm: 1 N: 43. B:2 N: 73. 6. Nb: 1. lymphoblasts. E. Lic: 0. Lab. Hem.9. E: 3. the number of false-positive samples was decreased in ABX Pentra DX120. monocytosis and large immature cells. E: 19 N:73. Causes of false-positive and false-negative results by Sysmex XE-2100 and ABX Pentra DX120 Sysmex XE-2100 False-positive Total (n = 119.8. B.

. 656–662. 45–54. 596–601. however.. Buttarello M.J..M. Accordingly. Harris R. ´ M. Clinica Chimica Acta 346.. The manual counts on these 11 samples. (2002) How useful are CBC and reticulocyte reports to clini- cians? American Journal of Clinical Pathology 118. (2008) Automated blood cell counts.9% in our laboratory for the period August 2009– July 2010. A College of American Pathologists Q-Probes Study of 95141 complete blood count determinations performed in 263 institutions. & Murphy M. Optimization of manual blood smear review criteria in a high-volume automated hematology laboratory.. Hart D. (2005) Reticulocyte Thome hemoglobin measurement: comparison of two methods in the diagnosis of iron restricted erythropoiesis. Wilkinson D. Oguni S. the slide-making rules could not be constructed equally in different analyzers and the slidemaking rates therefore varied. (2009) Performance of automated slidemakers and stainers in a working laboratory environment – routine operation and quality control. 83–90. 11. if the slide-making rates are variable among different hematology analyzers. Sandhaus L.. except for one sample with 3% basophils.M. Briggs C. Our study has several limitations. Renner N. Davis G. International Journal of Laboratory Hematology 32. McFadden S. Gascon-Lema M. Franck S. Considering that automated slide preparation triggers MSR. 2006).C. REDUCED SLIDE REVIEW IN HEMATOLOGY LABORATORY 7 results by ABX Pentra DX120 were considered falsenegative. 871–879. In summary. Simson E. Hem. Harrison P. & Toffolo L. & Thomas C.. Ó 2011 Blackwell Publishing Ltd. MSR.. Manual slide review to validate the results from automated hematology analyzers is currently an inevitable work process in clinical hematology laboratories.. Briggs C. (2003) Elimination of instrumentdriven reflex manual differential leukocyte counts. Lab. 93–99.. 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