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International Journal of Laboratory Hematology

The Official journal of the International Society for Laboratory Hematology

ORIGINAL ARTICLE INTERNATIONAL JOURNAL OF LA BO RATO RY HEMATOLOGY

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 SUMMARY


Medicine, Konkuk University
School of Medicine, Seoul, Korea Introduction: The validation of automated hematology analyzer results

Konkuk University, Seoul, Korea by manual slide review (MSR) is currently an inevitable work process
Correspondence: in clinical hematology laboratories. The laboratory workload would
Mina Hur, Department of be optimized if the requirement for MSR could be reduced without
Laboratory Medicine, Konkuk compromising patient care. We investigated whether slide-making
University School of Medicine, rates would be different between two hematology analyzers, which
Konkuk University Hospital, 4-12,
Hwayang-dong, Kwangjin-gu, were paired with their own automated slide makers/stainers: Sysmex
Seoul 143-729, Korea. XE-2100 with SP-1000i (Sysmex, Kobe, Japan) and ABX Pentra
Tel.: +82 2 2030 5581; DX120 with SPS evolution (ABX-Horiba, Montpellier, France).
Fax: +82 2636 6764;
E-mail: dearmina@hanmail.net
Methods: A total of 943 samples were run in parallel on the Sysmex
XE-2100 and ABX Pentra DX120. Reflex slides were automatically
This work was supported by made in each analyzer according to its own criteria, which reflected
Konkuk University in 2010. the criteria of MSR in our laboratory. The slide-making rates were
doi:10.1111/j.1751-553X.2011.01306.x
compared, and the results were further confirmed using the criteria
of MSR.
Received 24 September 2010; Results: The slide-making rates in Sysmex XE-2100, ABX Pentra
accepted for publication 21
DX120, and manual review were 22.5% (212/943), 15.91% (150/
December 2010
943), and 11.5% (108/943), respectively. In 774 (82.1%) samples,
Keywords
the three methods showed concordant results, and all made slides in
Slide, review, Sysmex XE-2100, 82 samples. Using the manual method as a standard, the sensitivity
ABX Pentra DX120, hematology 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.

requested tests in clinical laboratories. Technical evo-


INTRODUCTION
lutions in automated hematology analyzers have
The complete blood count (CBC) with leukocyte dif- improved the analytic performance greatly and have
ferential counts (LDC) is one of the most frequently broadened the range of information provided (Buttarello

434  2011 Blackwell Publishing Ltd, Int. Jnl. Lab. Hem. 2011, 33, 434–440
M. HUR ET AL. REDUCED SLIDE REVIEW IN HEMATOLOGY LABORATORY 435

& Plebani, 2008). Among the traditional CBC parame-


MATERIALS AND METHODS
ters, the red blood cell count (RBC), hemoglobin con-
centration (Hb), white blood cell count (WBC), and A total of 943 patient samples were randomly selected
mean cell volume generally show excellent analytical from the daily routine workload of our hematology
function, while the results for reticulocytes, platelet laboratory and were run in parallel on the Sysmex
counts, or certain components of LDC are less satisfac- XE-2100 and ABX Pentra DX120. Reflex slides were
tory (Buttarello, 2004; Segal et al., 2005). The clinical automatically prepared by each analyzer according to
applications and analytical function of the newly its own criteria, which were programmed to reflect
introduced parameters, such as reticulocyte indices, the criteria of MSR in our laboratory. To increase the
immature reticulocyte fraction, reticulated platelets, or clinical sensitivity, the criteria in each analyzer were
immature granulocytes, have not yet been fully estab- developed not to miss any pathological samples. The
lished or standardized (Buttarello et al., 2002; Sand- slide-making rates were compared between the two
haus & Meyer, 2002; Briggs et al., 2004; Thomas et al., analyzers, and the results were further confirmed with
2005). those of manual review. One expert senior technolo-
Despite the high-quality performances and gist checked all the CBC data and reflex slides that
expanded capabilities of automated analyzers, the were automatically prepared from each analyzer and
manual examination of blood smears still plays an slide maker/stainer combination to choose the slides
important role in hematology laboratories. Each labo- to be reviewed. Using the manual review as a stan-
ratory has its own decision-making criteria or rules dard, the sensitivity and specificity of each analyzer
for the validation of quantitative abnormalities or were obtained.
qualitative alterations that are highlighted (flagged) The decision-making criteria for MSR in our labo-
and which trigger slide preparations and reviews as ratory are presented in Figure 1. The Sysmex XE-2100
reflex tests (Lantis et al., 2003; Barnes et al., 2005). is used as the main hematology analyzer in our labo-
The laboratory workload and efficiency of generating ratory, and the workflow of slide review was devel-
the final CBC report are widely affected by the num- oped according to the use of this analyzer and its
ber of manual slide review (MSR) performed and are automated slide makers/stainer, the SP-1000i
variable between laboratories (Novis et al., 2006). Lab- (Figure 2). One of the criteria for slide review was to
oratory work processes would be optimized if the review all the samples from the hematology depart-
number of MSR could be reduced without compro- ment regardless of CBC abnormalities. Accordingly, in
mising patient care. addition to the main workflow of slide preparation
Automated slide makers and strainers, together through SP-1000i, we needed another process to iden-
with their hematology analyzers, are widely used in tify samples from the hematology department, for
high-volume hematology laboratories (Simson, Gas- which slides were not prepared. For such samples,
con-Lema & Brown, 2009). In such situations, reflex slide preparation and staining were performed manu-
slides are automatically prepared after the generation ally. The rules for slide making in the Sysmex XE-
of abnormal CBC data, with no manual intervention 2100 are listed in Table 1, and the workflow of the
by experienced laboratory staff. Although each labora- rules in ABX Pentra DX120 is summarized in Figure 3.
tory has criteria that trigger reflex slides, the imple- The main differences in the rules between the Sysmex
mentation of these criteria in the different XE-2100 and ABX Pentra DX120 were that depart-
hematology analyzers could vary according to the ment information and delta check could be included
characteristics of each analyzer. Consequently, the in the criteria for the ABX Pentra DX120.
rates of slide preparation and review might be highly To compare the diagnostic performances of Sysmex
affected. This study investigated whether the slide- XE-2100 and ABX Pentra DX120, their sensitivities
making rates were different between two hematology and specificities were analyzed using MedCalc Soft-
analyzers that were paired with their own automated ware (version 11.2.1; MedCalc Software, Mariakerke,
slide makers/stainers: Sysmex XE-2100 with SP-1000i Belgium). The statistical differences in their sensitivi-
(Sysmex, Kobe, Japan) and ABX Pentra DX120 with ties and specificities were obtained with chi-square
SPS evolution (ABX-Horiba, Montpellier, France). test.

 2011 Blackwell Publishing Ltd, Int. Jnl. Lab. Hem. 2011, 33, 434–440
436 M. HUR ET AL. REDUCED SLIDE REVIEW IN HEMATOLOGY LABORATORY

Figure 1. The decision-making criteria for manual slide review.

Figure 2. Workflow of slide review with Sysmex XE-2100 and SP-1000i.

22.5% (212/943), 15.91% (150/943), and 11.5%


RESULTS
(108/943), respectively. All the three methods showed
The comparison data of slide preparation by Sysmex concordant results in 774 (82.1%) samples: all posi-
XE-2100, ABX Pentra DX120, and manual review tive in 82 samples and all negative in 692 samples.
are presented in Table 2. The slide-making rates in Discrepant results were observed in 169 samples. No
Sysmex XE-2100, ABX Pentra DX120, and MSR were case showed a positive result by manual review but

 2011 Blackwell Publishing Ltd, Int. Jnl. Lab. Hem. 2011, 33, 434–440
M. HUR ET AL. REDUCED SLIDE REVIEW IN HEMATOLOGY LABORATORY 437

Regarding false-negative results, the causes were


Table 1. The rules for slide making in Sysmex XE-2100
department (n = 11) and absence of result (n = 4) in
Quantitative abnormalities Sysmex XE-2100, and absence of flag (n = 11) in ABX
Leukocytopenia/leukocytosis: WBC < 2.0 · 109/l or Pentra DX120. The quantitative values or flags in 11
WBC > 20 · 109/l samples with false-negative results by ABX Pentra
Neutropenia/neutrophilia: neutrophils < 30% or
DX120 are presented in Table 5. The Sysmex XE-2100
neutrophils > 85.5%
Lymphocytopenia/lymphocytosis: <10% or >70% also showed flags and/or quantitative abnormalities
Monocytosis: monocytes > 15.5% that triggered MSR in these 11 samples. However,
Eosinophilia: eosinophils > 20% these did not correspond to our criteria for the
Basophilia: basophils > 2% manual confirmation, except for one sample with 3%
Nucleated RBCs > 2/100 WBCs basophils (sample 8).
Thrombocytopenia/thrombocytosis: PLT < 100 · 109/l or
PLT > 600 · 109/l
Flags DISCUSSION
PLT clumps or abnormal distribution
Fragments The manual examination of blood smears is time-con-
Blasts suming and expensive and may not be always neces-
Immature granulocytes
sary. To increase the clinical sensitivity, most
Left shift
Atypical lymphocytes laboratories tend to develop less strict criteria so as
Abnormal lymphocytes/lymphoblasts not to miss potentially important abnormalities. This
would be more conspicuous especially when a hospi-
WBC, white blood cell count; RBC, red blood cell count; tal has a large pool of hemato-oncological patients.
PLT, platelet count.
According to the College of American Pathologists’
Q-Probes Study with 263 participating institutions,
negative results by both Sysmex XE-2100 and ABX the rates of MSR varied considerably among partici-
Pentra DX120. However, there were discrepant results pants (26.7% in the median, 9.9% in the 10th per-
between the Sysmex XE-2100 and ABX Pentra DX120 centile, and 50.0% in the 90th percentile institutions)
in 26 samples with positive MSR results: 15 were Sys- and were elevated with increased numbers of hospital
mex negative and Pentra positive and the other 11 beds (Novis et al., 2006). That study showed that the
were Sysmex positive and Pentra negative. Using rates of MSR were directly related to the efficiency in
MSR as a reference method, the sensitivity and speci- generating CBC results. Most of the MSR were trig-
ficity were 86.1% (95% confidence interval (CI), gered by hematology analyzer flags, and these thresh-
78.1–92.0%) and 85.8% (95% CI, 83.2–88.0%) in old limits also varied widely among participants.
Sysmex XE-2100 and 89.8% (95% CI, 82.5–94.8%) Recently, the use of automated slide makers and
and 93.7% (95% CI, 91.8–95.2%) in ABX Pentra stainers has increased in large-sized clinical laborato-
DX120, respectively (Table 3). Significant differences ries. They are used in combination with their multipa-
in the specificity and specificity of the analyzers were rameter hematology analyzers, and their performances
observed, with a difference of 3.7% (95% CI, 0.69– are reported to be comparable to well-prepared man-
6.71; P = 0.0165) for sensitivity and 8.0% (95% CI, ual processes (Simson, Gascon-Lema & Brown, 2009).
5.2–10.8; P < 0.0001) for specificity (chi-square test). Compared with manual procedures, the introduction
The causes of false-positive and false-negative of automated slide makers and stainers has signifi-
results were analyzed (Table 4). In the 119 samples cantly reduced the workload of slide preparation as
with false-positive results by Sysmex XE-2100, slide well as the turn-around-time of the final CBC report.
flag was the most frequent cause followed by delta On the other hand, not all the automatically prepared
check and department; slide flag and/or delta check slides are reviewed manually. If slide-making rules of
comprised three-quarters (75.7%) of the total false- the instrument do not perfectly match the slide-review
positive causes. In ABX Pentra DX120, the two causes criteria of the laboratory, there may be a discrepancy
of false-positive results were slide flag (64.2%) and between the prepared slides and reviewed slides. Con-
monocytosis with large immature cells (35.8%). sidering the general policy of laboratories not to miss

 2011 Blackwell Publishing Ltd, Int. Jnl. Lab. Hem. 2011, 33, 434–440
438 M. HUR ET AL. REDUCED SLIDE REVIEW IN HEMATOLOGY LABORATORY

Figure 3. Workflow of the rules for slide making in Pentra DX120. PDX, ABX Pentra DX120; SPS, SPS evolution;
PML, Pentra multilink data management system.

Table 2. Slide preparation by Sysmex XE-2100, ABX Table 3. Comparison of the results between Sysmex
Pentra DX120, and manual review XE-2100, ABX Pentra DX120, and manual review

Sysmex ABX Pentra Manual Number Sysmex XE-2100 ABX Pentra DX120
XE-2100 DX120 review (%)
Positive Negative Positive Negative
Positive Positive Positive 82 (8.7)
Positive Negative Positive 11 (1.2) Manual review
Negative Positive Positive 15 (1.6) Positive 93 15 97 11
Negative Negative Positive 0 (0) (n = 108)
Negative Negative Negative 692 (73.4) Negative 119 716 53 782
Positive Negative Negative 90 (9.5) (n = 835)
Negative Positive Negative 24 (2.5)
Positive Positive Negative 29 (3.1)

Positive means the slide preparation, and negative vice each hematology analyzer, and consequently, the gap
versa. between the prepared and reviewed slides may be dif-
ferent. To the best of our knowledge, no study has
focused on this practical issue in routine hematology
any possible pathologic samples, the presence of these laboratory so far.
unnecessarily prepared slides might be regarded as This study investigated whether the slide-making
inevitable. However, construction of the rules to rates would be different between two hematology
reflect the laboratories’ own criteria may be variable in analyzers when paired with their own automated slide

 2011 Blackwell Publishing Ltd, Int. Jnl. Lab. Hem. 2011, 33, 434–440
M. HUR ET AL. REDUCED SLIDE REVIEW IN HEMATOLOGY LABORATORY 439

Table 4. Causes of false-positive and false-negative results by Sysmex XE-2100 and ABX Pentra DX120

Sysmex XE-2100 ABX Pentra DX120

False-positive Total (n = 119, 100%) Total (n = 53, 100%)


Slide flag (n = 46, 38.7%) Slide flag (n = 34, 64.2%)
Delta check (n = 34, 28.6%) Mono + Lic (n = 19, 35.8%)
Department (n = 21, 17.6%)
Slide flag and delta check (n = 10, 8.4%)
Department and delta check (n = 8, 6.7%)
False-negative Total (n = 15, 100%) Total (n = 11, 100%)
Department (n = 11, 73.3%) No flag (n = 11, 100%)
No result (n = 4, 26.7%)

Mono + Lic, monocytosis and large immature cells.

Table 5. Quantitative values or flags in samples with false-negative results by ABX Pentra DX120

Quantitative values (%) or flags

Dep ABX Pentra DX120 Sysmex XE-2100 Manual differential count (%)

1 IM Lic: 1.0 Abn L/L-Blasts N: 67, Nb: 2, L: 25, M: 6


2 IM E: 16.9 Eosinophilia, Blasts N: 65, L: 8, M: 8, E: 19
3 IM No flags Abn L/L-Blasts N:73, L:16, M:6, E:3, B:2
4 IM Lic: 1.0 Aty L N: 73, Nb: 2, L: 17, M: 4, E: 1, B: 2, Aty L: 1
5 IM Lic: 2.2 Immature Granulocytes N: 78, Nb: 2, L: 12, M: 4, E: 2, B: 1, Mm: 1
6 IM M:13.6, Lic: 0.4, Aty L: 1.5 Abn L/L-Blasts N: 43, Nb: 1, L: 39, M: 13, E: 3, B: 1
7 IM nRBC, platelet aggregates, Basophilia N: 65, Nb: 1, L: 22, M: 7, E: 4, B: 1
monocytosis, (M: 11.4,
Lic: 0.6, Aty L: 1.4)
8 IM Lic: 0.8, Aty L: 0.9 Blasts N: 46, Nb: 2, L: 43, M: 6, B: 3
9 PED Neutropenia (M: 10.2, Neutropenia, N: 15, Nb: 4, L: 64, M: 11, E: 3, B: 2, Aty L: 1
Lic: 0.8, Aty L: 2.2) Abn L/L-Blasts
10 IM Lic: 2.0, Aty L: 1.7 Aty L N: 79, Nb: 4, L: 10, M: 5, B: 1, Aty L: 1
11 IM M: 12.8, Lic: 0.9, Aty L: 1.4 Aty L N: 61, L: 25, M: 9, E: 2, Aty L: 3

Dep, department; IM, internal medicine; PED, pediatrics; Lic, large immature cells; Aty L, atypical lymphocytes; Abn L,
abnormal lymphocytes; nRBC, nucleated RBCs; L-Blasts, lymphoblasts; N, neutrophils; Nb, band-form neutrophils; L,
lymphocytes; M, monocytes; E, eosinophils; B, basophils; Mm, metamyelocytes; My, myelocytes.

makers/stainers: Sysmex XE-2100 with SP-1000i and XE-2100 (Table 4). ‘Department’ was also the main
ABX Pentra DX120 with SPS evolution. Our data cause of false-negative results in Sysmex XE-2100,
showed that the sensitivity and specificity of slide and in the routine practice of our laboratory, this was
preparation were different between these two systems one of the main causes of extra workload.
and that the performance of ABX Pentra DX120 Eleven samples showed false-negative results by
with SPS evolution was superior to that of Sysmex ABX Pentra DX120 with no flags. In contrast, they
XE-2100 with SP-1000i (Table 3). In particular, the mostly showed flags of blasts, atypical lymphocytes, or
number of false-positive samples was decreased in immature granulocytes and/or quantitative abnormali-
ABX Pentra DX120, and the main causes of difference ties by Sysmex XE-2100 (Table 5). According to our
were attributable to ‘delta check’ and ‘department’, decision-making criteria for slide review, MSR was
which could not be included in the rules for Sysmex triggered by the results of Sysmex XE-2100, and the

 2011 Blackwell Publishing Ltd, Int. Jnl. Lab. Hem. 2011, 33, 434–440
440 M. HUR ET AL. REDUCED SLIDE REVIEW IN HEMATOLOGY LABORATORY

results by ABX Pentra DX120 were considered false- Manual slide review to validate the results from
negative. The manual counts on these 11 samples, automated hematology analyzers is currently an inevi-
however, showed that the review process was not nec- table work process in clinical hematology laboratories,
essary for most of the samples, except for one sample and the efficiency of generating CBC results may be
with 3% basophils. Accordingly, the actual false-nega- affected by how to set both instrument threshold trig-
tive rate of ABX Pentra DX120 would be lower and gers and laboratory policies (Novis et al., 2006). Despite
the specificity would be higher than the obtained data. suggested criteria, the criteria for MSR seem to be still
Our study has several limitations. It was conducted variable across laboratories (Barnes et al., 2005). The
to compare the slide-making rates between the two use of automated slide makers and stainers has
analyzers, but the rules of ABX Pentra DX120 were decreased manual workload and increased laboratory
constructed in accordance with our decision-making efficiency. Considering that automated slide prepara-
criteria, in which the pre-existent Sysmex XE-2100 tion triggers MSR, if the slide-making rates are variable
played a main part. Accordingly, MSR, a reference among different hematology analyzers, it would
method, might have itself affected the comparison directly affect the slide-review rate in the laboratory.
data possibly toward increased false-negative results Such an impact would be greater in high-volume labo-
by ABX Pentra DX120. Another limitation is that the ratories, especially if there is a large pool of hemato-
manual review rate in this study (108/943, 11.45%) oncological patients. In summary, our data showed
was relatively lower than the usual review rate in our that, even with the same laboratory criteria for slide
laboratory. The average manual review rate was review, the slide-making rules could not be con-
26.9% in our laboratory for the period August 2009– structed equally in different analyzers and the slide-
July 2010, ranging from 20.0% to 39.0%. It can be making rates therefore varied. This study implies that
explained by the fact that, for this study, we avoided in addition to the automation of slide preparation,
the busiest day of the week and the busiest time of there is a room for further optimization of laboratory
the day, although we tried to conduct it as a routine workload and efficiency by adjusting the slide-making
practice. This bias might have decreased the difference rate to each laboratory’s situation. More comprehen-
in slide-making rates and affected the causes of dis- sive effort is required to streamline the workflow and
crepant results. improve the productivity in hematology laboratories.

automated methods for performing immature cians? American Journal of Clinical Pathology
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