wg-pre recommendations for managing hemolyzed sampleslippi g, cadamuro j, danese e, gelati m,...

EFLM WG-PRE recommendations for managing hemolyzed samples

Ana-Maria Šimundić

Faculty of Pharmacy and Biochemistry, Zagreb University,

Zagreb, Croatia

Department of Medical Laboratory Diagnostics, University

Hospital Sveti Duh, Zagreb, CROATIA

o How frequent is hemolysis?

o What is the effect of hemolysis?

o What is wrong with visual detection of the degree of hemolysis?

o Situation in Europe?

o How reliable are manufacturer’s declarations?

o What has EFLM WG-PRE done to help?

The outline of my talk

The frequency of hemolysis?

How big is the problem?

Out of all rejected samples in a chemistry lab, hemolysis accounts for:

a) 3%

b) 10%

c) 40%

d) 60%

e) 90%

Q1

Hemolysis is the most frequent

laboratory error

Jones BA, Calam RR, Howanitz PJ. Chemistry specimen

acceptability: a College of American Pathologists Q-

Probes study of 453 laboratories. Arch Pathol Lab

Med. 1997;121(1):19-26.

o CAP, Q-probes, 1995 o 453 labs (434 from US) o data were collected for the reasons for 37,963 sample rejections

Hemolysis is the most frequent

laboratory error

Simundic AM, Nikolac N, Vukasovic I, Vrkic N. The prevalence of preanalytical errors in a Croatian ISO 15189 accredited laboratory. CCLM 2010;48(7):1009-14.

o all samples received over 1-year period were analysed

o from January 2008 until December 2008.

Frequency depends on the collection

facility

Lippi G, Salvagno GL, Favaloro EJ, Guidi GC. Survey on the prevalence of hemolytic specimens in an academic hospital according to collection facility: opportunities for quality improvement. Clin Chem Lab Med. 2009;47(5):616-8.

Hemolysis is more frequent in collections involving syringes and

catheters

Carraro P, Servidio G, Plebani M. Hemolyzed specimens: a reason for rejection or a clinical challenge? Clin Chem. 2000;46(2):306-7.

Hemolysis is associated with the pressure in the blood collection tube

Mrazek C, Simundic AM, Wiedemann H, Krahmer F, Felder TK, Kipman U, Hoppe U, Haschke-Becher E, Cadamuro J. The relationship between vacuum and hemolysis during catheter blood collection: a retrospective analysis of six large cohorts.

CCLM 2017;55(8):1129-1134.

The effect of hemolysis?

Fernandez et al. Harmonization in hemolysis detection and prevention. A working group of the Catalonian Health Institute (ICS) experience. CCLM. 2014;52(11):1557-68.

Assay- and instrument-specific effect

Nordic hemolysis project. DEKS, Equalis, ISLM, Labquality, NKK and Noklus. 2014. (http://deks.dk/pr/Nordic_Hemolysis_project_2014.pdf)

Bais R. The effect of sample hemolysis on cardiac troponin I and T assays. Clin Chem. 2010;56(8):1357-9.

Ortho Eci

Roche Elecsys

Assay- and instrument-specific effect

How do you detect the degree of hemolysis in your lab?

a) Visual check

b) Automated HIL indices

c) A combination of both

Q2

(for chemistry assays)

What is wrong with visual detection of hemolysis?

Visual inspection is highly unreliable and inconsistent

Comparability between visual and

automated detection is poor

Simundic AM, Nikolac N, Ivankovic V, Ferenec-Ruzic D, Magdic B, Kvaternik M, Topic E. Comparison of visual vs. automated detection of lipemic, icteric and hemolyzed specimens: can we rely on a human eye? CCLM 2009;47(11):1361-5.

Comparability between assessors

is low

Simundic AM, Nikolac N, Ivankovic V, Ferenec-Ruzic D, Magdic B, Kvaternik M, Topic E. Comparison of visual vs. automated detection of lipemic, icteric and hemolyzed specimens: can we rely on a human eye? CCLM 2009;47(11):1361-5.

CONCLUSIONS: Visual inspection of lipemic, icteric and hemolyzed samples is highly unreliable and should be replaced

by automated systems that report serum indices.

o retrospective study o emergency chemistry laboratory (data collected in 2015) o visual assessment + manual handling and management o re-assesment for all samples received in the period of 1

week

1/3 of all samples

incorrectly handled

Luksic AH, Nikolac Gabaj N, Miler M, Dukic L, Bakliza A, Simundic

AM. Visual assessment of hemolysis affects patient safety.

CCLM 2018;56(4):574-581.

cTnT, K and bilirubin most critical errors

Luksic AH, Nikolac Gabaj N, Miler M, Dukic L, Bakliza A, Simundic AM. Visual

assessment of hemolysis affects patient safety. CCLM 2018;56(4):574-581.

Risk analysis according to ISO 14971 standard: Application of Risk Management to Medical Devices

Situation in Europe?

Part 1. how laboratories in Europe monitor preanalytical phase and how data from this monitoring is currently used.

Part 2. detection and management of hemolysis, lipemia and icterus

1,405 responses from 37 European countries. o Primary care laboratory (18%) o Hospital laboratory (38%) o Laboratory that serves both in-

and out-patients (40%)

WG-PRE survey

Biochemia Medica, 2019; in press

High proportion (14%) of labs still

do not monitor HIL

Cadamuro J, et al. European survey on preanalytical sample handling – Part 2: Practices of European laboratories on monitoring and processing hemolytic, icteric and lipemic samples. On behalf of the EFLM WG-PRE. Biochemia Medica 2019: in press

HIL indices are monitored by 86% of the 1,347 respondents who stated to analyze blood samples


How do you measure the degree

of hemolysis, lipemia and icterus

in your lab? visual detection

30%

both

28% 42%

automated HIL indices

High proportion of labs still perform visual HIL check


Yes

No

Those who perform a visual check…

Majority of labs do not even use a color scale for a visual HIL

check


1 g/L

no answer

0.5 g/L

0.1 g/L

0.3 g/L

We use different cut-offs to define

hemolysis


We manage hemolyzed samples

differently


Automated HIL detection,

followed by a visual check and

individual decision

Individual decision only, based on visual check

same cut-offs for all analytes

parameter specific cut-offs provided by the manufacturer

in-house developed analyte specific cut-offs

We use different cut-offs to manage

hemolyzed samples

Are manufacturer’s declarations reliable? Useful? Safe?

o Bias is not evidence based (biological variation/clinical significance of the test)

o Most use 10% bias as allowable deviation (or 3SD) o Instead of continous data, just a single cut-off is provided

(5g/L)

Ref 3: CLSI/NCCLS, Interference Testing in Clinical Chemistry, EP7-P, 1986

Nordic hemolysis project. DEKS, Equalis, ISLM, Labquality, NKK and Noklus. 2014. (http://deks.dk/pr/Nordic_Hemolysis_project_2014.pdf)

Manufacturer’s declarations often can

not be verified in the lab

Fernandez P, et al. Harmonization in hemolysis detection and prevention. A working group of the Catalonian Health Institute (ICS) experience. CCLM 2014;52(11):1557-68.

Nikolac N, Simundic AM, Miksa M, Lima-Oliveira G, Salvagno GL, Caruso B, Guidi

GC. Heterogeneity of manufacturers' declarations for lipemia interference--an

urgent call for standardization. Clin Chim Acta. 2013 Nov 15;426:33-40.

The aim: to verify the manufacturers' specifications for lipemia interference for clinical chemistry reagents provided by Beckman Coulter, Roche and Siemens.

Nikolac N, Simundic AM, Miksa M, Lima-Oliveira G, Salvagno GL,

Caruso B, Guidi GC. Heterogeneity of manufacturers' declarations for

lipemia interference--an urgent call for standardization.

Clin Chim Acta. 2013;426:33-40.

The aim: to verify the manufacturers' specifications for lipemia interference for clinical chemistry reagents provided by Beckman Coulter, Roche and Siemens.


Yes, all of them

No

Yes, some of them

Majority of the labs do not verify

manufacturer’s declarations

o hemolysis is the most common preanalytical error o it affects many analytes o our practices are heterogeneous and not

standardized o this creates the risk of reporting wrong results

To summarize…

Opportunity for diagnostic errors (missed, delayed or wrong diagnosis)

We have to do

something about it

Lippi G, Simundic AM, Rodrigues-Manas L, Bossuyt P, Banfi P. Standardizing in vitro diagnostics tasks in clinical trials: a call for action. Ann Transl Med 2016, doi: 10.21037/atm.2016.04.10

Solution?

Standardize the way we detect and manage hemolyzed samples

Producing and systematically using the evidence based, patient oriented guidelines, rules, and specifications

What has EFLM WG-PRE done to help?

Lippi G, Cadamuro J, von Meyer A, Simundic AM. Practical

recommendations for managing hemolyzed samples in clinical chemistry

testing. Clin Chem Lab Med. 2018;56(5):718-727

AIM: To suggest a pragmatic approach for managing results of clinical chemistry testing in hemolyzed samples.

Lippi G, Cadamuro J, von Meyer A, Simundic AM. Practical recommendations for managing hemolyzed samples in clinical chemistry testing. Clin Chem Lab Med. 2018;56(5):718-727

Are you using IQC for HIL indices in your lab?

a) Yes, I use commercial controls

b) Yes, I prepare my own pool

c) No

Q3

Lippi G, Cadamuro J, von Meyer A, Simundic AM. Local quality assurance of serum or plasma (HIL) indices. Clin Biochem. 2018;54:112-118. 1.

The aim: to provide an expert opinion about management of internal quality control (IQC) assessment for HIL indices.

Lippi G, Cadamuro J, von Meyer A, Simundic AM. Local quality assurance of serum or plasma (HIL) indices. Clin Biochem. 2018;54:112-118. 1.

o we support the use of in-house prepared IQC materials

o we give you advice on how to prepare pools for IQC materials

o at least 2 levels for each interfering substance should be used

o IQC testing for HIL indices should be performed at least 2 times per day in routine and stat laboratories

o IQC testing should be systematically recorded

o IQC should be interpreted and acted upon in the same manner as with any other IQC result

Lippi G, Cadamuro J, Danese E, Gelati M, Montagnana M, von Meyer A, Salvagno GL, Simundic AM. Internal quality assurance of HIL indices on Roche Cobas c702. PLoS One. 2018;13(7):e0200088.

von Meyer A, Cadamuro J, Lippi G, Simundic AM. Call for more transparency in

manufacturers declarations on serum indices. Clin Chim Acta. 2018;484:328-332.

This document aims to propose some reliable solutions that may be adopted by manufacturers for increasing worldwide harmonization of serum indices.

EFLM WG-PRE proposal

von Meyer A, Cadamuro J, Lippi G,

Simundic AM. Call for more transparency in

manufacturers declarations on serum

indices. Clin Chim Acta. 2018;484:328-332.

o How frequent is hemolysis?

o What is the effect of hemolysis?

o What is wrong with visual detection of the degree of hemolysis?

o Situation in Europe?

o How reliable are manufacturer’s declarations?

o What has EFLM WG-PRE done to help?

The outline of my talk

“Amid all of the pressing priorities, we must remember that the elimination of harm to our patients and workforce is our foremost

moral and ethical obligation.”

Gary S. Kaplan, MD, FACMPE Charles D. Stokes, RN, BSN, FACHE

Co-Chairs of the Leading a Culture of Safety Project

http://safety.ache.org/pledge-and-assessment/

Arthur Ashe was the first black tennis player who was selected to the

United States Davis Cup team and the

only one ever to win the singles title at

Wimbledon, the US Open, or the

Australian Open.

“Start where you are. Use what

you have. Do what you can.”

– Arthur Ashe

July 10, 1943 – February 6, 1993

https://due.com/blog/start-where-you-are-arthur-ashe/

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