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PostScript

CORRESPONDENCE
Clinical consequences of
erroneous laboratory results
that went unnoticed for
10 days
Erroneous laboratory results can adversely
affect medical decisions. While the preva-
lence of laboratory errors has been well
documented,1 their consequences, particu-
larly when they go unnoticed, are less well
reported. We describe the clinical conse-
quences of a series of falsely elevated labora-
tory results that went unnoticed for 10 days.
On 20 June 2012, an endocrinologist
alerted the laboratory to possible spurious
results after noticing extremely high
insulin-like growth factor-1 (IGF-1) con-
centrations in two clinically asymptomatic
patients. The ensuing investigations
revealed an error in the analyser
(Immulite 2000, Siemens, Surrey, UK) that
performed five endocrine tests, including
IGF-1, and affected all results reported on
11 June. The error eluded the internal
quality control (QC) testing performed
routinely prior to patient sample analysis.
All erroneous results (n=63) were
unknowingly reported. Retesting of all speci-
mens belonging to 49 patients revealed 2.1-
to >108-fold reductions in their results (see
online supplementary table S1). The ranges
of the erroneous results and the correct
values (in parentheses), respectively, were:
adrenocorticotrophic hormone (ACTH,
n=10), 15.3–132 pmol/l (<1.11–36.6);
anti-thyroglobulin antibodies, 67–
>3000 IU/ml (n=15, <20–830); anti-
thyroid peroxidase antibodies, 37–
>1000 IU/ml (n=7, <10–876); growth
hormone, 2.12–188 mg/l (n=10, 0.35–
9.63); IGF-1 603–2263 ng/ml (n=21, 54–
292). All ordering physicians were immedi-
ately notified of the amended results. The
engineers of the manufacturer were immedi-
ately brought in to conduct an extensive
investigation, which included checking for
reagent/probe/tubing contamination, reagent

Table 1 Laboratory results, potential and actual clinical consequences of the patients affected by the erroneous laboratory results
Purpose of Laboratory Erroneous Corrected Actual clinical
Case Primary diagnosis testing test Units results results Potential clinical consequence consequence

1 Autoimmune thyroid Diagnostic ATG IU/l >3000 404 Repeat testing None
disease on carbimazole work-up ATPO IU/l >1000 876 TSH: <0.02 mIU/l
Free T4: 16.6 pmol/l
2 Syncope Diagnostic ATG IU/l 69 <20 None None
work-up ATPO IU/l 691 150 TSH: 6.90 mIU/l
Free T4: 16.6 pmol/l
3 Partial empty sella Disease IGF-1 ng/ml 1509 55 Repeat testing Repeat testing
monitoring
4 Pituitary microadenoma Disease GH mg/l 38.5 2.09 MRI imaging for suspected GH secreting Repeat testing
monitoring IGF-1 ng/ml 614 130 adenoma
5 Automimmune thyroid Disease ATG IU/l 96 <20 Erroneous results not seen by physician None
disease monitoring ATPO IU/l 277 13
6 Vitreous haemorrhage Diagnostic ATG IU/l 92 <20 None None
work-up ATPO IU/l 37 <10 TSH: 0.86 mIU/l
Free T4: 16.8 pmol/l
7 Hypoadrenalism Diagnostic ACTH pmol/l 41.1 2.1 Misdiagnosis as primary hypoadrenalism Adrenal CT-scan
ordered
8 Congenital adrenal Disease ACTH pmol/l 102 36.6 Misdiagnosis of poor compliance to None
hyperplasia monitoring glucocorticoids
9 Hypothyroidism on Diagnostic ATG IU/l 126 23 Misdiagnosis of Hashimoto’s disease None
L-thyroxine replacement work-up ATPO IU/l 366 <10 and need for repeat testing
TSH 0.05 mIU/l
Free T4: 18.4 pmol/l
10 Grave’s disease Diagnostic ATG IU/l 300 <20 None None
work-up ATPO IU/l >1000 49 TSH: <0.02 mIU/l
Free T4: 12.7 pmol/L
11 Automimmune thyroid Disease ATPO IU/l >1000 191 None None
disease monitoring
12 Hypoglycaemia for Diagnostic GH mg/l 39.5 2.16 Misdiagnosis of acromegaly None
investigation IGF-1 ng/ml 765 178
Repeat mg/l 6.82 0.97
testing ng/ml 783 180
GH
IGF-1
13 Metastatic thyroid cancer Disease ATG IU/l 97 <20 None None
monitoring
14 Thyroid cancer, Disease ATG IU/l >3000 28 Misdiagnosis of cancer recurrence, need None
post-surgical removal monitoring for further laboratory and imaging
studies
15 Thyroid cancer, Disease ATG IU/l 140 <20 Misdiagnosis of cancer recurrence, need None
post-surgical removal monitoring for further laboratory and imaging
studies
The free thyroxine and thyrotropin concentrations measured together with the thyroid auto-antibody tests are provided.
ACTH, adrenocorticotrophic hormone (reference interval: 0.0–10.2 pmol/l), ATG, anti-thyroglobulin antibodies (negative if <40 IU/l), ATPO, anti-thyroid peroxidase antibodies (negative if
<50 IU/l), GH, growth hormone (male <3.00 mg/l; female <8.00 mg/l), IGF-1, insulin-like growth factor-1 (87–238 ng/ml), free T4, free thyroxine (10.0–23.0 pmol/l), TSH, thyrotropin,
(0.45–4.50 mIU/l).

260 J Clin Pathol March 2013 Vol 66 No 3

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probe/tubing blockage, pipetting accuracy
and incubation temperature. No offending
cause was identified. The error was attribu-
ted to an ‘isolated random event’ by the
manufacturer. We have since replaced the
faulty instrument. Further, the medical
records of all the patients (n=15) belonging
to our institution for whom we have access
to their case notes, were reviewed after
receiving institutional approval (DSRB/E/
2012/00509) (table 1).
All but one patient’s result were already
seen by the physicians when errors were
notified. Seven (47%) of the tests were per-
formed for diagnostic purposes while the
rest were for disease monitoring. The erro-
neous results could have potentially affected
the diagnostic and/or management deci-
sions of nine patients. Two patients (cases 3
and 4) had repeat IGF-1 testing as the
initial results were questioned by the order-
ing physicians. In another case (case 7), an
erroneously high ACTH value (reported
value 41.1 pmol/l, corrected result
<2.0 pmol/l) resulted in the misdiagnosis
of primary hypoadrenalism, for which a
CT scan of the adrenals was arranged. This
was however cancelled after the laboratory
error was notified to the primary physician.
For the remaining patients, there were no
changes in clinical management due to the
high index of suspicion of the original diag-
nosis by the treating physicians.
Five patients (cases 1, 2, 6, 9, 10) who
newly presented to our institution had
their thyroid auto-antibodies measured as
part of their diagnostic work-up. Cases 1
and 9 who presented with hyperthyroid-
ism (on carbimazole) and hypothyroidism
(on L-thyroxine), respectively, were
referred for further work-up and specialist
care. The erroneously high thyroid auto-
antibodies would have suggested the pres-
ence of auto-immune thyroid disease and
Hashimoto’s disease, respectively. In our
practice, the thyroid auto-antibody tests in
these patients would have required repeat
testing. Additionally, the erroneously high
titres of anti-thyroglobulin antibodies that
were previously undetectable in cases 14
and 15 could have led to a misdiagnosis
of thyroid cancer recurrence since their
baseline serum thyroglobulin concentra-
tions were undetectable.2
Despite automated processes, rigorous
QC measures and improved assays,
laboratory testing remains susceptible to
errors.1 This report highlights the vulner-
ability of relying on routine QC testing
alone for error detection. In this instance,
a member of staff who was not clinically
trained and had insufficient experience
failed to recognise the unusual pattern of
laboratory results and proceeded to verify
J Clin Pathol March 2013 Vol 66 No 3
the erroneous results since the internal
QCs were ‘in control’. The laboratory
results are not routinely reviewed by clin-
ically qualified staff prior to reporting.
The internal QC rules used were the
Westgard 13S and 22S rules.
We have since strengthened our staff
training, increased supervision and put in
place competency testing before allowing
laboratory staff to independently verify
laboratory results. The competency train-
ing included educating the staff on the
basic clinical biochemistry/physiology of
the analytes, the general caution of when
to suspect laboratory errors (eg, use of
delta-checks, extreme values, having
results that are all biased in one direction).
These were incorporated into our revised
standard operating procedures. Less
experienced staff are also required to
undergo a period of shadowing for
1.5 months. A few written scenarios are
used to assess the staff at the end of the
competency training as well as during their
yearly competency testing. An additional
mid-day internal QC was also instituted.
Where resources permit, additional mea-
sures to strengthen the QC include: use of
rule-based systems and the requirement of
two laboratory staff to independently
verify results. For example, the use of rule-
based systems may alert the laboratory staff
to unusual patterns of laboratory results,
such as unusually large changes between
consecutive laboratory results (delta-
checks) and supra-physiological results
(extreme values). The second member of
laboratory staff, preferably someone with
more experience, may act as an additional
safeguard against missed errors.
This report also reminds physicians to
remain vigilant against possible erroneous
results and discuss clinically incongruent
results with the laboratory personnel.
Finally, communicating laboratory errors is
challenging.3 When laboratory errors are
detected, the primary (requesting) phys-
ician should be informed quickly so that
corrective measures can be undertaken,
thereby preventing unnecessary, expensive
and potentially harmful interventions (eg,
ionising radiation from a CT scan for case
7 in our series). Finally, medical errors
remains sparsely reported in the literature
and should be encouraged to facilitate dis-
cussions about patient safety issues and
improve clinical practice.4
Tze Ping Loh,1 Lennie Chua Lee,2 Sunil
Kumar Sethi,1 Doddabele Srinivasa Deepak2
1
Department of Laboratory Medicine, National
University Hospital, Singapore
2
Division of Endocrinology, Department of Medicine,
National University Hospital, Singapore
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Correspondence to Dr Tze Ping Loh, Department of
Laboratory Medicine, National University Hospital, 5
Lower Kent Ridge Road, Singapore 119074; lohtp@
yahoo.com
▸ Additional supplementary files are published online
only. To view these files please visit the journal online
(http://dx.doi.org/10.1136/jclinpath-2012-201165).
Contributors TPL conceived, collected the data and
co-wrote the first draft. LCL and DSD managed the
patient. DSD co-wrote the first draft. SKS critically
reviewed and revised the final draft.
Competing interests None.
Ethics approval Domain Specific Review Board of the
National University Hospital, Singapore.
Provenance and peer review Not commissioned;
externally peer reviewed.
To cite Loh TP, Lee LC, Sethi SK, et al.
J Clin Pathol 2013;66:260–261.
Received 24 August 2012
Revised 10 October 2012
Accepted 15 October 2012
Published Online First 6 November 2012
J Clin Pathol 2013;66:260–261.
doi:10.1136/jclinpath-2012-201165
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2 Kim WG, Yoon JH, Kim WB, et al. Change of serum
antithyroglobulin antibody levels is useful for
prediction of clinical recurrence in
thyroglobulin-negative patients with differentiated
thyroid carcinoma. J Clin Endocrinol Metab
2008;93:4683–9.
3 Dintzis SM, Stetsenko GY, Sitlani CM, et al.
Communicating pathology and laboratory errors: anatomic
pathologists’ and laboratory medical directors’ attitudes
and experiences. Am J Clin Pathol 2011;135:
760–5.
4 Murphy JG, Stee L, McEvoy MT, et al. Journal
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 Downloaded from http://jcp.bmj.com/ on March 24, 2015 - Published by group.bmj.com

Clinical consequences of erroneous

laboratory results that went unnoticed for 10
days
Tze Ping Loh, Lennie Chua Lee, Sunil Kumar Sethi and Doddabele
Srinivasa Deepak

J Clin Pathol 2013 66: 260-261 originally published online November 7,

2012
doi: 10.1136/jclinpath-2012-201165

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