Haemolysis

Laboratory management of
haemolysed samples – results
of an RCPAQAP survey
Penny Petinos
Agenda
 Background to KIMMS survey on haemolysis
 Results of the 2010 and 2014 surveys
 Outcomes/decisions
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Background to KIMMS survey
 KIMMS data consistently showed that haemolysis was one of the top 3
reasons why laboratories reject a sample/test
 There is little published data on how laboratories manage haemolysed
samples
 To determine current practice in Australian laboratories for
haemolysed samples
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Summary data 2010
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Summary data 2013
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Survey 4 2014 data
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What information should be captured?
 What policies exist to manage haemolysed samples (report/results)
 Where does the problem originate?
 How is haemolysis determined (manually/electronically)?
 What does the laboratory do to minimise/reduce haemolysed
samples?
 Is there a need for guidelines from the industry (RCPA/AACB or other
professional bodies) on how to manage haemolysis?
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Definition of Haemolysis
Haemolysis: the breakdown of erythrocytes in blood, which frees the
haemoglobin and intracellular contents from the cells.
NOTE: Serum or plasma prepared from hemolysed blood has visible red color when
released haemoglobin exceeds 200mg/L (20 mg/dL). The serum or plasma concentrations
of other abundant red cell components such as potassium, phosphate and lactate
dehydrogenase also may be increased.
CLSI Haemolysis, Icterus, and Lipemia/Turbidity Indices as Indicators
of interference in Clinical Laboratory Analysis: Approved Guideline
CLSI document C56- A Wayne, PA. Clinical and Laboratory Standards
Institute; 2012
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Haemolysis
 Studies have shown that pre-analytical errors are quite significant and
haemolysis is the most predominant interference, in pathology laboratories.
Carraro P, Plebani M. Errors in a stat laboratory; types and frequencies 10 years later. Clinical Chemistry
2007; 53(7): 1338-1342
 Haemolysis can interfere with accurate measurement of some analytes in
serum or plasma. In particular, lactate dehydrogenase (LD) concentration
may be 160 times greater, potassium may be 22 times greater and
magnesium up to 3 times greater in a haemolysed sample.
CLSI Haemolysis, Icterus, and Lipemia/Turbidity Indices as Indicators of interference in Clinical Laboratory Analysis:
Approved Guideline CLSI document C56- A Wayne, PA. Clinical and Laboratory Standards Institute; 2012
 Moderate haemolysis can influence the reliability of haemostasis results
Lippi G, Montagnana M, Salvagno GL, Guidi GC. Interference of blood lysis on routine coagulation
testing. Arch Pathol Lab Med 2006; 130(2): 181-4
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Agenda
 Background to KIMMS survey on haemolysis
 Results of the 2010 and 2014 surveys
 Outcomes/decisions
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Results from 2010 and 2014
 The 2010 survey was quite comprehensive
 All Australian participants were invited to complete the survey
(Chemical Pathology/Haematology/Transfusion/Microbiology etc.)
 Huge amount of data collected, report issued over a year later
 Survey conducted again in 2014 to compare results and identify any
significant changes to policies/management of haemolysis
 2014 survey not as extensive as the previous survey
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2010 Survey Data
Data submitted
by 332
laboratories,
shown here by
discipline
Genetics
General Pathology (multidisciplinary)
Microbiology/Serology
Transfusion
Immunology
Haematology
Anatomical Pathology/Cytopathology
Clinical Chemistry
0.0%
10.0%
20.0%
30.0%
40.0%
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Demographics
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Causes of Haemolysis
Table – Major causes of
haemolytic specimens in
clinical laboratories
(European Preanalytical
Scientific Committee,
EPSC. Available at:
www.specimencare.com)
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In vivo haemolysis
 It is important to note that in vivo haemolysis is a cause of
haemolysed samples and it is vital to identify this as the cause of the
haemolysis, as soon as possible. In vivo haemolysis can be caused by
several disease states including haemolytic anaemia.
 Where in vivo haemolysis is suspected, it is advisable to differentiate
the cause of the haemolysis as rejecting these samples may delay
treatment to for the patient and monitoring of the disease.
Haemolysis as influence and interference factor, Thomas L, eJFCC vol 13 no 4: http://www.ifcc.org/ejifcc/vol13no4/130401002.htm
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Causes of haemolysis
Studies conducted in the US indicate that haemolysis was higher in
samples collected by an iv catheter and the number of haemolysed
samples may be reduced by collecting blood samples via venepuncture
Kennedy C, Angermuller S, King R, Noviello S, Walker J, Warden J, Vang S. A comparison of haemolysis rates using
intravenous catheters versus venepuncture tubes for obtaining blood samples. J Emerg Nurs. 1996; 22(6):566-9.
Lowe G, Stike R, Pollack M, Bosley J, O'Brien P, Hake A, Landis G, Billings N, Gordon P, Manzella S, Stover T. Nursing blood
specimen collection techniques and hemolysis rates in an emergency department: analysis of venipuncture versus
intravenous catheter collection techniques. J Emerg Nurs. 2008 Feb;34(1):26-32. Epub 2007 Sep 25.
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Causes of Haemolysis
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Reporting haemolysis data outside
pathology
It was interesting to note that
60-64% of laboratories do not
report haemolysis rates to
those outside the laboratory,
despite widespread knowledge
that the causes of haemolysis
occurs during collection,
transport and
processing/storage of samples.
The data shows most
haemolysis originating from
areas outside the control of the
laboratory, with the exception
of collection centres (the 2010
data may reflect changes to the
deregulation of collection
centres around that time).
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Investigating haemolysis
 Any failures in the total testing process should be investigated by laboratories
conducting root cause analysis of problems. Where the root cause analysis identifies a
particular area of concern, then it makes sense to communicate the problems to
those areas and work with that area to reduce haemolysis rates, where possible.
 By reducing haemolysis, laboratories can prevent negative impact to patient care
regardless of whether the error was caused by the laboratory or outside the
laboratory.
Plebani M, The detection and prevention of errors in laboratory medicine. Annals of
Clinical Chemistry. 2010; 47: 101-110
 Some KIMMS participants do report the data to specific wards and relevant quality
meetings within their organisation and they have reported reductions in haemolysis rates.
It is important to stress that this is a continuous improvement process.
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Determining in vitro Haemolysis
Visual detection of haemolysis is quite a subjective and unreliable method. In
recent times, manufacturers have introduced Haemolysis Index (HI) reporting for
analysers. The main advantage to Haemolysis Index reporting is that it overcomes
the subjectiveness of visual haemolysis reporting and provides a level of
standardisation in the reporting of haemolysis.
Haemolysis as influence and interference factor, Thomas L, eJFCC vol 13 no 4:
http://www.ifcc.org/ejifcc/vol13no4/130401002.htm
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Recording haemolysis
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Recording haemolysis
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Cut off values
It was impossible to
determine the most
commonly used cut off
for haemolysis as the
results were reported in
various units, other
than those requested.
Referring to the 2010
data, values vary from
1-5000.
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HI as indicator of pre-analytical quality
The haemolysis index (HI) is a (semi)quantitative estimate of free haemoglobin and provides a
marker or alert to haemolysis interference.
In some systems the HI closely approximates the range of haemoglobin concentrations within the
haemolysis index. These systems usually monitor absorbance of serum or plasma at various
wavelengths.
Automated haemolysis index can be used to provide a numerical value that can be used to assess
the integrity and quality of the sample. The numerical value can then be utilised to set ‘cut-off’
values for rejecting a sample.
CLSI Haemolysis, Icterus, and Lipemia/Turbidity Indices as Indicators of interference in Clinical Laboratory Analysis: Approved Guideline
CLSI document C56- A Wayne, PA. Clinical and Laboratory Standards Institute; 2012
Plebani and Lippi suggest ‘consideration should be given to routine reporting of serum indices along
with the results of individual analytes’ and that ‘objective measures of sample integrity such as the
serum indices would offer considerable benefits for quality management’.
Plebani M, Lippi G. Hemolysis index: quality indicator or criterion for sample rejection? Clinical
Chemistry & Laboratory Medicine 2009; 47(8):899-902
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HI as indicator of pre-analytical quality
Söderberg et al considered the use of the haemolysis index as a measure of preanalytical quality. Their study measured haemolysis in a number of primary
healthcare settings and reports that Emergency Departments ‘stood out’ as
significant contributors to haemolysed samples.
Although they used a low cut off of 0.15mg/L of free haemoglobin, they were able
to show haemolysis rates were 6 times higher in some primary health settings than
others. The haemolysis rate in primary healthcare settings was 10.4% compared to
31.1% in Emergency Departments. The authors were able to show that haemolysis
index can be a useful measure of pre-analytical quality.
Söderberg J, Jonsson P.A, Wallin A, Grankzist K, Hultdin J. Haemolysis index – an estimate of preanalytical quality
in primary health care. Clinical Chemistry & Laboratory Medicine 2009; 47(8):940-944
KIMMS inlcudes rejection rates for haemolysed samples as one of the key quality
indictors in the pre-analytical phase.
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Comments from 2010 survey
 Any haemolysed coagulation samples are rejected.
 Biochemistry samples rejected if Haemolysis index >200. Run and reported with affected tests deleted if
haemolysis index >100. If haemolysis index between 40 and 100, automatic comment added to report.
Haematology samples rejected if biochemistry haemolysis index >200
 Haemolysis commenting and specimen rejection is based on multivariant criteria. This is subjective
based on such criteria as the urgency, difficulty or likelihood of recollection or clinical worth of a value
 If a precious sample is haemolysed results are reported with an appropriate comment depending on the
assay requested but only if the interference is less than +/- 10%, e.g. Report Potassium as less than the
analysed result
 For difficult to recollect samples such as paediatric or off site collections a result may be reported with a
qualifying statement
 A corrected result is issued only for our Emergency department up to a certain H index, once exceeded
results are rejected When recollect is easy, for example on hospital ward, recollect will be organised.
When haemolysed sample is a pathology staff collect, at any location, a recollect is organised. When
haemolysed sample is a GP collect, sample is run and haemolysis index is used
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Haemolysis Rejection Policy
 Participants were surveyed to determine if they had a policy on
reporting results on haemolysed samples.
 In 2010 81% of respondent indicated they had a Haemolysis Rejection
policy compared to 90% in 2014.
 There is still approximately 10% of respondents to the survey
indicating they have no formal policy on reporting results on
Haemolysed samples
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Survey data on haemolysis policies
Response
Response % 2010
Response % 2014
Rejects all haemolysed SAMPLES, i.e. all tests on a haemolysed sample
10.5
6.5
Rejects all haemolysed SAMPLES (as above), except precious or
irreplaceable samples
10.5
4.8
REJECT TEST results depending on Instrument Haemolysis Index or other
assessment of haemolysis interference
68.9
83.9
Perform the test and report TEST RESULTS, WITH QUALIFYING statement
that the sample was haemolysed
45.7
27.4
Perform the test and report TEST RESULTS, WITHOUT QUALIFYING
statement
3.8
1.6
Haemolysed comment and single ESTIMATE of analytical result reported
3.5
1.6
Haemolysed comment and ESTIMATED RANGE of analytical result reported
3.2
1.6
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Haemolysis rejection policy
The CLSI guidelines while stating it is the responsibility of the laboratory to reject and/or report results of a
haemolysed sample, does not provide guidance on how to report or annotate a result from a haemolysed
sample.
A survey of Italian laboratories on pre-analytical variables showed that;
 54% of laboratories perform testing and report results with a ‘Haemolytic’ comment in the report
 27% do not process the samples (and request a repeat sample)
 16% do not test the sample and include a ‘Haemolytic’ comment and
 3% process the sample and correct the result for the haemolysis.
This survey demonstrated the variation in reporting of results on haemolysed samples and the apparent
lack of policies on haemolysed samples.
Lippi G, Montagnana M, Giavarina D, National survey on the pre-analytical variability in a representative
cohort of Italian laboratories. Clinical Chemistry & Laboratory Medicine 2006; 44(12): 1491-1494
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Conclusions
 The survey data indicates significant variability in the way laboratories
reject and report results on heamolysed samples
 It was difficult to draw any conclusions from this data, other than to
highlight the variability in practices, which appears to have improved
from 2010 to 2014
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Agenda
 Background to KIMMS survey on haemolysis
 Results of the 2010 and 2014 surveys
 Outcomes/decisions
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Outcomes
 RCPAQAP has approached AACB to consider forming a Working Party to develop
guidelines for ‘Recommendations for reducing haemolysis of samples’
 It would be useful if the AACB working party can define the exact level that
analytical interference starts to be seen and then laboratories can report a rate of
haemolysis that is comparable.
 KIMMS data can be used to raise awareness of unsafe work practices so targeted
solutions can be implemented to improve patient safety. A recent example of
KIMMS data utilisation is the need for best practice standards for collection of
pathology samples. This has been addressed by the ‘Best Practice Pathology
Collection Project’.
Pilbeam, V., Badrick, T. and Ridoutt, L. (2013) Best practice pathology collection for Department of Health,
Canberra, Australia.
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Best Practice Pathology Collection
To establish best practice pathology collection both the service (customer focus)
and technical (laboratory focus) processes are considered and is established by
three components:
1. A consensus on the technical aspects or procedure that is undertaken by
pathology collectors when collecting blood from a vein.
2. Structured quality assurance systems linked to accredited management
standards such ISO 15189, in conjunction with laboratory systems to detect
errors in samples; and
3. Assessing and maintaining competence of pathology collectors (including
customer service competencies) through training programs that develop the
correct skills and techniques required and can provide a structure from which to
assess individual competence and benchmark practice
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Outcomes – evidence based decisions
The Centre for Health Systems and Safety Research, Australian Institute of Health
Innovation, UNSW, in collaboration with RCPAQAP KIMMS has undertaken a study
with the aim of;
 Comparing the reported frequency and prevalence, risk and detection variability
for haemolysed specimens
 Measure the levels of haemolytic specimens involving Troponin from Emergency
Departments (ED) and the number of tests not reported, and
 Investigate the measures employed by a group of pathology laboratories to
identify variation and their impact on the quality and effectiveness of laboratory
processes
The study will provide real data on the impact these incidents have on patients and
the risk associated with these incidents, from a quality health care perspective.
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Outcomes
Findings;
 Haemolysis rate was 3 times higher from the Emergency Department than
other hospital departments
 The Emergency Department length of stay was increased when the sample
was haemolysed
 5.3% of specimens collected for a Troponin test were haemolysed and there
were 11, 983 repeat Troponin tests
 Risk factors associated with haemolysis in hospitals; there was a higher rate
of haemolysis in the very young and elderly patients, in females compared to
males, specimens collected by non-phlebotomy staff and specimens collected
on weekends
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Acknowledgements
 RCPAQAP KIMMS Advisory Committee
 Stephanie Gay – KIMMS Project Officer
 Department of Health, Quality Use of Pathology
Program (QUPP) for funding of the KIMMS
Program
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