lipid metabolism and cardiac test markers: …jccls.org/seminar_record/2010/03.pdf · lipid...

Lipid Metabolism and Cardiac Test

Markers:

Importance of Standardization

Barbara M. Goldsmith, Ph.D., FACB

Vice President, Marketing, Membership

and Education

Clinical and Laboratory Standards

Institute (CLSI)

Outline of Presentation

• CLSI Background Information

• Standards and Guidelines

• Lipid Standardization and Traceability

• Cardiac Markers and Risk Assessment

• Summary

2

Our Common Goal: Quality Healthcare

CLSI Background

• Established in 1968

• Nonprofit organization based in the United States

• American National Standards Institute (ANSI)–

accredited standards-development organization

• Volunteer driven through our governance structure

and technical operations

• An organization of organizations

• More than 200 standards and guidelines

CLSI Name

Name change in 2005 to reflect global constituencies

CLSI’s Vision

To be the leader in clinical and

laboratory standards to improve

the quality of medical care.

CLSI’s Mission

To develop best practices in clinical and laboratory

testing and promote their use throughout the world,

using a consensus-driven process that balances

the viewpoints of industry, government, and the

health care professions.

CLSI Today

• $7M annual budget

• 45 employees

• 2,000 member organizations

• nearly 2,000 active volunteers (>600

Non-North American memberships, >70

countries)

• consensus standards and guidelines

• >75,000 documents each year distributed

CLSI Consensus Process

9

Professions

Balance

Industry

Government

CLSI consensus process

• Meetings are open to everyone

• Meeting materials are fully available

• Balanced interests

• Conflicts of interest are fully disclosed

• Appeals process

• All comments addressed

CLSI products

• Standards

• Guidelines

• Collections

• Videos

• Toolkits

• Reports

• ISO documents

• Developed in conjunction with Analyse-it®

Software

• Only software to faithfully implement the

eight most popular CLSI method evaluation

guidelines

• Evaluates and verifies performance

characteristics of laboratory methods

• Provides clear step-by-step advice on

performing a study

• Delivers tools for accreditation

preparedness

• Easy-to-use workflow

• Provides timely, accurate statistical results

• Professional reports, customizable graphs

and charts

New method evaluation software

Benefits

• Large hospital laboratories

• Small hospital laboratories

• Physician office laboratories

• Reference laboratories

• In vitro diagnostic customer

support departments

Use of CLSI Documents

• Regulatory Compliance- Compliance with recognized CLSI consensus documents to facilitate regulatory review of IVD devices.

• Professional Practice - Implementation of CLSI best practices for accreditation preparedness

• Education in Clinical Laboratory Sciences

• Translations include: - Japanese -Spanish

- Korean (In progress) -Turkish

- Portuguese -Chinese (In progress)

- Russian - German

Adoption of Documents into Accreditation

Process – Example of Crosswalk

14

CLSI Members & Volunteers

15

Diverse representation from three constituencies

Industry Government Professions

IVD Manufacturers Public Health Agencies Hospitals and Laboratories

LIS Vendors Regulatory Bodies Healthcare Delivery Systems

Startup Companies Accrediting Organizations Educational Institutions

Suppliers Others Professional Societies

Trade Organizations

CLSI Area Committees

• Automation and

Informatics

• Clinical Chemistry and

Toxicology

• Evaluation Protocols

• Hematology

• Immunology and Ligand Assay

• Microbiology

• Molecular Methods

• Point-of-Care Testing

• Quality Systems and Laboratory Practices

Global Health Partnerships

• Grant funding from U.S.

government

• 10 staff members

• More than 60 volunteers

qualified as trainers

17


CLSI Lab Strengthening Program Services:

• Assessment/Gap Analysis

• Training and Education

• Mentoring

• Laboratory Self-assessment

• Continuous Quality Improvement


Current programs planned

or underway in

- Côte d’Ivoire Mali

- Tanzania Azerbaijan

- Ethiopia Georgia

- Namibia Uzbekistan

- Vietnam Kazakhstan

- Nigeria Ghana

Preparing laboratories for

WHO-Afro accreditation

Cote

d'Ivoire

Nigeria

SenegalEthiopia

Rwanda

Botswana

CLSI’s Key Global Activities

International Organization for Standardization (ISO)

• CLSI is Secretariat for ISO Technical Committee 212

“Clinical Laboratory Testing and in vitro Diagnostic Test

Systems” and its working groups:

• CLSI is administrator of the ANSI-Accredited US

Technical Advisory Group (TAG) to ISO/TC 212.

WG 1: Quality and competence in the medical laboratory.

WG 2: Reference SystemsWG 3: In vitro diagnostic productsWG 4: Antimicrobial susceptibility testing

http://www.sist.si/slo/g2/img/iso_logo.gif

Relationship of CLSI and ISO Standards

Complimentary, not conflicting, roles

broad, standard

requirements

detailed help and

practical guidance



Standards and Guidelines

23

Standards & the Lab

• Most medical lab errors

are caused by systems

and process issues, not

people.

• They are the areas

where standards can

help the most.

Why do Standards Matter?

• Raise levels of quality, safety, reliability, efficiency, and interchangeability

• Lower trade barriers

• Act as a base for legislation (or avoid the need for legislation)

• Aid in technology transfer

• Provide easy access to best-in-class practices

• Deliver improved outcomes at an economical cost

25

Standards Development Consensus Process

A consensus standard or guideline is a

document developed to promote uniform

products, materials, methods, or practices.

Levels of the consensus process:

• Proposed Level

• Approved Level

26

Standard or Guideline?

• A standard must be followed exactly as written.

- Written using verbs such as will, must, and shall

• A guideline may be modified by the user.

- Written using verbs such as should, could, may,

or might

27

Standardization and Traceability

28

Reasons for testing

• To identify individuals at increased risk of disease and/or monitor disease management

• To develop epidemiologic data from which to establish public health strategies for disease management

G. Myers, CDC, with permission

Requirements to meet testing goals

• Precise and accurate assays

• Results must be comparable, independent of

where and when test performed and assay used

• Specific measurement standards of higher order

– Reference measurement procedure(s) (RMP)

– Reference laboratories that provide RMPs

– Reference material(s)

• Process or program to establish and maintain

traceability to established standards

G. Myers, CDC, with Permission

Standardization of Laboratory Results In the context of laboratory medicine we really

mean Metrological Traceability


Traceability: ISO Definition

• Traceability - property of the result of a

measurement or the value of a standard whereby it

can be related to stated references, usually national

or international standards, through an unbroken

chain of comparisons all having stated uncertainties.


Traceability in Laboratory Medicine

Tools Needed for Traceability

• Reference measurement procedure(s)

• Gold Standard

• Reference MP Laboratories

• Reference materials (commutable)


Traceability in Laboratory Medicine

Patient Sample Result

Routine MP Patient Sample Result

Reference Materials

(commutable)

process that ensures patient sample results by a routine

measurement procedure areequivalent to RMP results

RMP

Met

rolo

gica

l Tra

ceab

ility


Standardization vs. Proficiency Testing

• Standardization is NOT the same as proficiency testing (PT)– Most PT programs in the US are NOT accuracy-

based programs

– PT programs use peer-group grading where laboratories are evaluated using the group mean for a particular instrument/method

– Standardization programs must be accuracy-based and provide an analytical anchor for traceability purposes


To establish traceability and be standardized, a laboratory must be: Precise and Accurate

Precise, not accurate

Neither accurate nor precise

Precise and accurate

Accurate, not precise

RMP


When and Why Is Traceability Most

Important?

• To insure the reliability and comparability of

research findings across studies

• When patients are seen in a variety of health care

settings, each using different clinical labs

• When patient’s clinical test results are being

compared to guidelines from the medical literature

and/or large national or international research

studies (e.g., estimated GFR for CKD, HbA1c for

diabetes, cholesterol for CVD, etc.).


Three Separate Measurement Components that

Require Traceability to Reference Standards

• Research Laboratories that support

investigational studies

• Manufacturers that develop and provide routine

clinical assays

• Clinical laboratories that provide test results for

assessing risk and monitoring therapy


Calibration

Patient SampleCorrelation

Manufacturer

Clinical Lab.

2

Proficiency Testing

1 3

Commutable Samples

Calibration

Reference procedure

(GC-IDMS or LC-IDMS)

Reference Laboratories

Primary Calibrator

Calibration Traceability Scheme

SRM

G. Meyers

Metro

logical Trace

ability

NIST IDMS

CDC AK

CRMLN AK

Manufacturer

Clinical Laboratory

Patient

SRM 1951b 1º reference material

CDC 2º reference materials

Fresh sample comparison

Mfr working calibrator

QC and GLP

SRM 911 (pure cholesterol standard)

Cal

ibra

tio

n H

iera

rch

yTraceability Chain for Cholesterol Measurement


Reference Measurement Procedure, HDL & LDL

Beta-quantification

1. Ultracentrifuge

serum

3. Abell-Kendall Chol.(LDL + HDL) – HDL = LDL

Chylo

VLDL

LDL

HDL

Rem.

IDL

Lp(a)

Apo E

2. Hep/Mn++ precipitate

HDL

LDL


UC density cut

Hep-Mn ppt

Hep-Mn soluble

Lipoproteins include a range of particles

Used with permission

Beta-quantification limitations

• A range of lipoprotein particles are included in

HDL, LDL and VLDL fractions

• Consequently, the measurand is poorly defined

• Lipoproteins may be distributed differently in

diseased vs. normal serum

• A particular lipoprotein may be present in unusually

high proportion

• A lipoprotein that is normally a minor component may

be present in relatively high concentration


NCEP performance criteria

Total Error Bias* CV*

TC 9% 3% 3%

HDL-C 13% 5% 4%a

LDL-C 12% 4% 4%

TG 15% 5% 5%

*Suggested limits to meet TE requirement

a CV 4% at 42 mg/dL; SD 1.7 at 42 mg/dL

Clinical Chemistry 1988;34:193-201 (TC), and 1995;41:1414-1433 (HDL,LDL, TG)

NCEP = National Cholesterol Education Project

Trueness (accuracy) TraceabilityR

ou

tin

e M

eth

od

Reference Method

Patient Specimens

Ro

uti

ne M

eth

od

Reference Method

Patient Specimens

Manufacturer comparison with a CDC Network Reference Lab

Cannot mix calibrators and reagents from different manufacturers

Traceability to the reference system is through the

manufacturer’s method specific calibrators

Calibrator value

SIG

NA

L

Routine Method

Calibration

Reportable

patients’

results are

traceable

to


Lipids: method evaluation

• Precision

– CLSI EP5

• Bias vs. RMP using patient specimens

– CLSI EP9

• Interferences



• Interferences:

– Metabolites, drugs (e.g. Hb, bilirubin, ascorbate) that

cause a measurement interference

• CLSI EP7

– Distinguish between a measurement interference and a

physiologic effect

• E.g. bilirubin can cause spectrophotometric effect,

react with H2O2, and correlates with liver disease that

may produce an abnormal lipoprotein (e.g. LpX)



• Interferences:

– Method non-specificity is important

– Influence on physicochemical separation of lipoprotein molecular forms

• To normal lipoproteins in abnormal concentrations

• To abnormal lipoproteins

• To other proteins

• CLSI EP21 total error


HDL COLOR

Chol esterase

Chol oxidase

Dye

Peroxidase

Step 2: convert HDL-C to a measurable substance

Homogeneous HDL-C: approach 1

Chylo VLDL LDL

+ -+ -+ -

+ -

+ -

+ -+ - + -Y

Y

Y

Y

Step 1: prevent reaction of non-HDL-C

YY


Chol esterase

Chol oxidase

Catalase

Chylo VLDL LDLHDL NO COLOR

1. Protect HDL-C from reaction and convert non-HDL-

C to non-measurable substances

Homogeneous HDL-C: approach 2

++

-

-

HDL

Dye

PeroxidaseCOLOR

2. Un-protect HDL-C and convert to a measurable substance

HDL ++

-

-


+ -

Chylo VLDL HDL

+ -+ -+ -

+ -

+ -+ - + -

1. Protect non-LDL

LDL COLOR

Chol esterase

Chol oxidase

Dye

Peroxidase

2. Convert LDL-C

Homogeneous LDL-C: analogous to HDL-C

LDL

Chol esterase

Chol oxidase

Catalase

Chylo VLDL NO COLOR

1. Protect LDL and convert non-LDL-C

HDL

Dye

PeroxidaseCOLOR

2. Unprotect and convert LDL-C

LDLLDL

G. Meyers, CDC, with permission

Homogeneous measurement challenges

• Measure the same lipoprotein fractions that are

measured by beta-quant

• Not measure anything else

• Do it for a wide range of clinical conditions with

abnormal lipoproteins and other proteins

• Do it with acceptable total error for individual

samples (not just trueness and imprecision) and cost


Why is standardization important

clinically?

Comparison of HDL and LDL Cholesterol Methods

to Reference Measurement Procedures

Background:

• Current guidelines on use of LDL-C and HDL-C

for cardiovascular risk assessment based on early

epidemiologic studies that established link

between lipoproteins and cardiovascular disease

• Based on older methods that depended on

physical separation of different lipoprotein classes

and not direct methods

• Direct measurements prompted by NCEP panel

that stated LDL-C should be measured directly

54Miller WG et al Clin Chem 56:6 977-986 (2010)



• Methods from 7 manufacturers and 1 distributer for direct

measurement of HDL-C and LDL-C were evaluated for

imprecision, trueness, total error, and specificity in

nonfrozen serum samples

• 6 of 8 HDL-C and 5 of 8 LDL-C direct methods met NCEP

total error goals for non-diseased individuals

• Patients included individuals with and without disease and

patients with various types of lipoprotein disorders (unlike

previous studies)

• All methods failed to meet NCEP goals for diseased

individuals due to lack of specificity toward abnormal

lipoproteins

55Miller WG et al Clin Chem 56:6 977-986 (2010)



Authors’ Conclusions:

• NCEP accuracy goals based on laboratory testing when

guidelines were developed (e.g. precipitation-based

methods for HDL-C, Friedewald equations for LDL-C) and

clinical need to classify CHD risk and monitor lipid

treatment (drugs)

• Composition of lipoproteins in various dyslipidemias affect

direct methods in specifically measuring cholesterol

content of one lipoprotein class in presence of other

lipoproteins; challenging for manufacturers of direct

methods

56Miller WG et al Clin Chem 56:6 977-986 (2010



Authors’ Conclusions (Con’t)

• Cannot rule out interferences (drugs, co-

morbidities, triglycerides, nutrition, nonfasting

specimens)

• Differences between direct methods and RMPs

could affect diagnosis and clinical management of

patients

• 30-45% test results outside of NCEP total error

goals for some methods; could reduce overall

effectiveness of screening for CV risk assessment

57Miller WG et al Clin Chem 56:6 977-986 (2010

Cardiac Markers and Guidelines

National Academy of Clinical Biochemistry (NACB)

Laboratory Medicine Practice Guidelines (LMPG)

Published NACB LMPGs

• Therapeutic Drug Monitoring 1999

• Cardiac Markers 1999

• Hepatic Injury 2000

• Diabetes Mellitus 2002

• Thyroid Disease (2nd edition) 2002

• Tumor Markers in the Clinic 2003

• Emergency Toxicology 2005

• Maternal-fetal Risk Assessment 2006

• Biomarkers of ACS 2007 *

• Point of Care Testing 2007

• Tumor Marker Quality Requirements 2009

• Expanded Newborn Screening 2009

• Emerging Biomarkers for CV Risk Factors 2009 *

• Major Tumor Markers 2009

• Pharmacogenetics 2010

• Liver Tumor Markers 2010

61

NACB LMPG:

Biomarkers of Acute Coronary

Syndrome (ACS)

(Published 2007)

Steps to consider in evaluating

Biomarkers

• Is concentration different in persons affected by

disease in comparison to those not affected

• Is there a body of evidence from case-control and

prospective studies that have evaluated the test

• Does measurement improve ability to assess risk

above and beyond current approaches

• Are there reliable analytical methods available for

measurement

62NACB LMPG, ACS, 2007

Risk Stratification of Acute Coronary

Syndromes (ACS)

• Tools:

– History and physical

– Standard ECG and non-standard ECG leads

– Cardiac biomarkers (Troponin I or T, CK-MB, Myoglobin, others)

– Predictive indices/schemes (better as research tools than for real-time decision-making)

– Non-invasive imaging studies (echo, stress test)

NACB LMPG, ACS, 2007

NACB Guideline Recommendations (selected

recommendations for ACS)

• Biomarkers of myocardial necrosis should be measured in all patients who present with symptoms consistent with ACS

• Cardiac troponin is the preferred marker for the diagnosis of MI. CK-MB by mass assay is an acceptable alternative when cardiac troponin is not available

• Blood should be obtained for testing at hospital presentation followed by serial sampling with timing of sampling based on clinical circumstances. For most patients, blood should be obtained at presentation, 6-9 hrs, and 12-24 hrs if earlier sample negative

Note – Recommendation Classes omitted

NACB Recommendations (Con’t)

• For patients who present within 6 hrs of onset of

symptoms, an early marker may be considered in

addition to troponin. Myoglobin is the most

extensively studied marker for this purpose

• Total CK, AST, beta-hydroxybutyric

dehydrogenase, and/or LD should NOT be used

as biomarkers for the diagnosis of MI


NACB Recommendations (Con’t)

• A cardiac troponin is the preferred marker for

risk stratification and, if available, should be

measured in all patients with suspected ACS. In

patients with a clinical syndrome consistent with

ACS, a maximal concentration exceeding the 99th

percentile of values for a reference control group

(with acceptable precision) should be considered

indicative of increased risk of death and recurrent

ischemic events


Troponin as a Marker of Increased Risk in

ACS

30%

12% 11%

34%

22%

19% 19%

23%

12%

6%6%

0%1%2%4% 4%

0%

10%

20%

30%

40%

Hamm

(1992)

FRISC

(1996)

TRIM

(1999)

Pettijohn

(1997)

Hamm

(1997)

Hamm

(1997)

Polanczyk

(1998)

Galvanni

(1997)

De

ath

or

MI

Troponin +

Troponin -

Strengths of Troponin as biomarker:

• Almost 100% sensitivity for acute MI with serial draws

• Cardio-specific• Remains elevated in circulation up to 7

days• Excellent for retrospective diagnosis of

acute MI• Best prognostic indicator for ACS


Limitations of Troponin

• Not an early marker

• No standardization of methods across

troponin I assays from different

manufacturers

• Sporadic elevations from minor myocardial

damage may confuse interpretation

NACB LMPG ACS, 2007

Not all Troponins are Alike

• Analytical recommendations (NACB Guidelines): 99th percentile with a CV <10%

• Troponin I-multiple manufacturers; issue with standardization

• Troponin T-only one manufacturer (Roche); no issue with standardization

• Cutoffs NOT interchangeable


FDA Approved Cardiac Troponin Assays

Myoglobin

• Early rising necrosis marker

• Rises within 1-3 hours of onset of ACS

• Doubles in concentration over a two hour

period

• Specificity of >95-98% for acute MI

• 2 negative results 2 hours apart rules out

acute MI in 97-99% patients


Limitations of Myoglobin

• Can be cleared in 6 hrs

• Present in cardiac and skeletal muscle

(non-specific)

• Elevated in muscle trauma and renal

dysfunction


Optimal TAT for Cardiac Biomarkers

for ACS

• NACB Recommendations:

– Laboratory should perform cardiac marker testing with

TAT of 1 hour, optimally 30 minutes or less.

• TAT defined as time from blood collection to the reporting of

results

– Institutions that cannot consistently deliver cardiac

marker TAT of 1 hour should implement POC platform

– Acceptable harmonization to central lab results should

be < 20%


NACB Recommendations-BNP

• Plasma BNP or NT-proBNP testing should be

performed to confirm the diagnosis of HF in

patients with suspected diagnosis, but with

presenting signs and symptoms that are

ambiguous with confounding disease (COPD)

• In diagnosis of patients with HF, routine plasma

BNP or NT-proBNP with obvious clinical diagnosis

is not necessary


BNP and NT-proBNP - NACB

Recommendations

• No primary reference materials are validated for

calibration of BNP or NT-proBNP. Harmonization

around the current presumed optimal diagnostic

medical decision cutoff of 100 pg/mL for BNP

should be validated. There is only one source of

antibodies and calibrators for NT-proBNP so

harmonization of NT-proBNP assays should not

be a problem


BNP and NT-proBNP – NACB

Recommendations

• Normal reference limits (95th or 97.5th percentile)

should be independently established for both BNP

and NT-proBNP based on age (by decade) and

by gender. Each commercial assay should be

validated separately. The effect of ethnicity needs

to be evaluated as a possible independent

variable


National Academy of Clinical

Biochemistry (NACB) Laboratory

Medicine Practice Guidelines

(LMPG):

Emerging Biomarkers for Primary

Prevention of Cardiovascular

Disease and Stroke

(Published 2009)

78

Emerging Risk Factors for

Cardiovascular Disease

• C-Reactive Protein

• Serum amyloid A

• Soluble CD-40 ligand

• Fibrinogen

• D-dimer

• Factovs V,VII,VIII

• Lipoprotein(a)

• LDL and HDL subtypes

• Homocysteine

• Microalbuminuria

• Cystatin C

• Apo E genotype

• Remnant lipoproteins

• Interleukins (eg, IL-6)

• Vascular and cellular adhesion

molecules

• Leukocyte count

• Plasminogen activator inhib 1

• Tissue-plasminogen activator

• Small dense LDL

• Apoliproproteins A1 and B

• Oxidized LDL

• Lipoprot-assoc phopholipaseA2

• Creatinine (GFR)

• Infectious agenst

• Fibrinopeptide A

• Von Willebrand factor antigen

79NACB LMPG Emerging Biomarkers for CVD 2009

Biomarkers and Cardiovascular Disease

Risk – NACB Guidelines

• Inflammation Biomarkers *

• Lipoprotein Subclasses and Particle

Concentration

• Lipoprotein (a)

• Apolipoproteins A-I and B *

• Markers of Renal Function

• Homocysteine *

• Natriuretic Peptides (BNP and NT-proBNP)

Inflammation Biomarkers and

Cardiovascular Disease Risk - hsCRP

High-sensivity C-Reactive Protein (hsCRP)

• Recommendation 1: After standard global risk

assessment, if the 10-year predicted risk is <5%,

hsCRP should not be measured

• Recommendation 2: If risk is intermediate (10-

20%) and uncertainty remains as to the use of

preventive therapies (statins or aspirin) then

hsCRP measurement might be useful for further

stratification into a higher or lower risk category

NACB LMPG , CVD, 2009

Inflammation Biomarkers and

Cardiovascular Disease Risk (Cont)

• Recommendation 3 – There are insufficient data

that therapeutic monitoring using hsCRP over

time is useful to evaluate effects of treatments in

primary prevention

• Recommendation 4 – The utility of hsCRP

concentrations to motivate patients to improve

lifestyle behaviors has not been demonstrated

• Recommendation 5 – Evidence is inadequate to

support concurrent measurement of other

inflammatory markers in addition to hsCRP for

coronary risk assessment

82NACB LMPG, CVD, 2009

Apolipoproteins A-I and B and

Cardiovascular Disease Risk

• Recommendation 1 – The first step to monitor

efficacy of lipid lowering therapies is to measure

LDL-C (and non-HDL-C) in patients with elevated

triglycerides

• Recommendation 2 – Although apoB measures

atherogenic lipoproteins and is a good predictor of

CVD risk (equal at least to LDL-C and non-HDL-

C), it is only a marginally better predictor than the

current lipid profile and should not be routinely

measured at this time for use in global risk

assessment


Apolipoproteins A-I and B and

Cardiovascular Disease Risk

• Recommendation 3 – Measurement of apo-B can

be used to monitor efficacy of lipid-lowering

therapies as an alternative to non-HDL-C

• Recommendation 4 – The apo B/apo A-I ratio can

be used as an alternative to the usual total

cholesterol/HDL-C ratio to determine lipoprotein-

related risk for CVD

• Recommendation 5 – Manufacturers of apo-B and

apo-A I assays should establish traceability to

accepted standards to assure reliable and

comparable results


Homocysteine (Hcy) and Cardiovascular

Disease Risk

• Recommendation 1 – Hcy concentrations (umol/L)

derived from standardized assays categorize

patients as follows:

– Desirable < 10

– Intermediate (low to high) >10 to <15

– High > 15 - <30

– Very high > 30


Homocysteine and Cardiovascular

Disease Risk

• Recommendation 2 – The analytical performance

goal for clinical usefulness for measurement of

Hcy should be <10% for bias, <5% for precision,

and <18% for total error. Manufacturers of

diagnostic assays for Hcy should follow approved

value transfer protocols to assure that

standardized assays are used for vascular risk

assessment


NACB LMPG

Point of Care Testing

(Published 2007)

Point of Care Cardiac Markers

• Benefits of cardiac marker POCT:

– Reduced bottleneck in the ED

– Identification of cardiac patients more quickly

– Reduce inappropriate treatment pathways

– Allow for more rapid rule-out of a cardiac event

– Reduction in LOS for chest pain, CHF, and MI

NACB Guideline Recommendations-”Evidence-

Based Practice for Point of Care Testing”: POC

Cardiac testing

• The laboratory should perform cardiac marker

testing (for the ED) with a TAT of 1 hour, optimally

30 minutes or less. TAT is defined as the time

from blood collection to the reporting of results

• Comments: timeframe required to determine need

for thrombolytic therapy. Rule out of MI requiring

serial samples diminishes the need for a very

rapid TAT on any single sample

NACB LMPG, POC, 2007

NACB POC Cardiac Marker

Recommendations (Con’t)

• Institutions that cannot consistently deliver cardiac

marker TAT of approximately 1 hour should

implement POC testing devices • Performance characteristics should not be

different between central laboratory and POC platforms

• While it is recognized that qualitative systems do provide useful information, it is recommended that POC systems provide quantitative results

NACB LMPG, POC, 2007

Summary

• CLSI is an internationally recognized, consensus-based

standards organization producing a large number of

documents and related materials

• Standards and Guidelines are essential in establishing

uniform good laboratory practices

• Standardization and traceability of methods allow

commutability of results and improve quality and clinical

care

• Although work has been done in areas of lipid and cardiac

marker standardization/harmonization, further work is

needed

91

Contact Information – Speaker

• Barbara M. Goldsmith, Ph.D., FACB

• Email: [email protected]

• Phone: 610-688-0100 Ext 112

• Address: 940 West Valley Road

Suite 1400

Wayne, Pennsylvania 19087 USA

92

mailto:[email protected]

THANK YOU FOR YOUR

ATTENTION

93