Total control of INR results: Certified plasmas with a web-based tool

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4HemosIL® ISI Calibrate4HemosIL INR Validate4ISIweb™ Application

Local IsI assignment and ValidationTheWorldHealthOrganization(WHO)adoptedtheInternational

NormalizedRatio(INR)in1983inanefforttoreducereagent

variationandimprovestandardization.TheInternationalSensitivity

Index(ISI)isameasureofareagent’sresponsivenesstoreduced

levelsofVitaminK–dependentfactorscomparedtoaprimary

InternationalReferencePreparation(IRP)ofalikesource.

ISIandMeanNormalProthrombinTime(MNPT)areusedto

determinetheINRvaluesofpatientsamples.

INR = (Plasma PT / MNPT)ISI

WhiletheINRsystemhassignificantlyimprovedPTreporting,it

isstillassociatedwithahighdegreeofvariationandinconsistency

amonglaboratories.ReliableINRdeterminationdependsupon

accurateISIandMNPTvalues.

ClinicalandLaboratoryStandardsInstitute(CLSI)and

InternationalSocietyonThrombosisandHaemostasis

(ISTH)(SSC)havepublishednewguidelinestoimprove

INRinterlaboratoryvariability.Incorporatingcertifiedplasmas

intheestablishmentofalocalISIhasconsiderablyreduced

inter-laboratoryimprecision.Thefollowingstepsinthe

guidelinesensureoptimalINRreporting:

• Use of certified plasmas

- Thecertifiedplasmasmaybecomposedofpooled,stable

Anti–VitaminKtherapy(AVK)donorsforlikenesstofresh

orartificiallydepletedplasma.

- Certifiedplasmas,traceabletoWHOInternationalReference

Preparations,areusedtoassignspecies-specificvalues,

correspondingtolocallaboratorythromboplastin.

• Verification of INR results

- INRresultsobtainedwiththemanufacturer’sISIandthe

localMNPTarecomparedwiththeINRvaluesofasetof

atleastthreelevelsofcertifiedplasma(INR1.5–4.5).

• Local system calibration

- AmodifiedWHOprocedurewhichdeterminesandplots

thelocalinstrument/reagentPTvaluesagainstthe

assignedvaluesofcertifiedplasmasonalog/logplot,using

orthogonalregressionanalysis,isperformed.Theresulting

analysisyieldsthenewlocalISIfromtheslope,andthe

newlocalMNPTfromtheinterceptofthisregressionline.

• Verification of INR results using new local system

calibration parameters

- ThenewlocalISIandMNPTareincorporatedintothe

locallaboratoryinstrumentandverifythatthenewlocal

ISIandMNPTcanbeimplemented.

TheCLSIandISTHguidelinesproposethateachlaboratoryverifytheuseofthecorrectISIwhen:

• changingthelotnumberofthethromboplastinreagent,

• amajorinstrumentcomponentisreplaced,

• laboratoryisnotincompliancewithanexternalqualityassessmentscheme.

Total Solution for Local ISI Assignment and Validation

HemosIL INR VaLIdate

HemosIL IsI CaLIbRate

IsIweb

• Tri-levelsetofcertifiedplasmas(madefromstablehumanAVKdonors)assessINRaccuracy.Reference

INRvaluesarereagent-specificandrangefrom1.6–5.0.

• Testonalocalinstrument/reagentsystemusingIL’sinstrument/reagent-specificISIandthelaboratory’s

establishedlot-specificMNPT.

• IftheINRvaluesare±15%oftheassignedreferencevalues,asdeterminedthroughISIweb,thePT/INR

systemisverified.

• Ifthemeanofanycontrollevel(INR)is>±15%oftheirassignedreferencevalues,asdeterminedthrough

ISIweb,anewlocalISIcalibrationisrecommendedusingHemosILISICalibrate.INRValidateisusedagain

toverifyanewlyestablishedlocalISIandMNPT.

• Setoffourcertifiedplasmas(levelANormalandlevelsB–DAbnormal).TheINRreferencevalueshavean

INRrangeof0.9–5.0.ThenormalplasmasaremadefromapoolofnormaldonorsandtheAVKplasmas

arefromstablehumandonorsundergoingAVKtherapy.

• TestonalocalILinstrument/reagentsystemandenterthePTsecondsintoISIweb,whichcomparesthem

toreferencevaluesbyplottinganorthogonalregressionofthelog/logplot.ThenewlocalISIandnewlocal

MNPTarederivedfromtheregressionline.

• Web-basedtoolavailabletoallILcustomersusingACLHemostasissystemsandHemosILPTreagents,

inconjunctionwithINRValidateandISICalibratekits,toverifylocalPT/INRsystemsand,ifnecessary,

establishnewlocalISIandMNPT(CLSIandISTHcompliant).

• ISIwebelectronicallyarchivesandreportsallactivitiesonlocalISIassignmentandvalidation—anessentialtool

forregulatorycomplianceandaccreditation.

ThiscompletediagnosticsolutionfeaturesINRValidate,ISICalibrateandthefirstself-guided,web-basedtool,ISIweb.

ItofferstotalcontroloverthelocalISIassignmentandvalidationprocessonILHemostasissystems,whenmonitoring

patientsundergoingoralanticoagulanttherapy.

• Easyandintuitivesystemforreportingqualitytestresults

• Increasedefficiencyinbenchmarkingstandardizedvalues

• MaximumperformanceofILHemostasissystems

IsI assignment and Validation overview

Uponregistration,eachlabcanperformthefollowingfunctions:

1.INRValidation: ToverifytheaccuracyoftheINR

2.LocalISIAssignment: ToestablishanewlocalISI

3. ValidationofLocalISI: ToverifynewlocalISIandnewMNPT

Step 1INR Validation

• RunINRValidate

(induplicateoverthree

sessions)

• EnterINRresultsinto

ISIweb

TheISIwebalgorithmwill

checkthatresultsarewithin

expectedvalues.

1.Pass:Continueusing

manufacturer’sISIand

localMNPT

2.Fail:ProceedtoStep2

Step 2Local ISI Assignment

• RunISICalibrate

(induplicateoverthree

sessions)

• EnterPTresults(sec)into

ISIweb

TheISIwebalgorithmwill

checkthatresultsarewithin

expectedvaluesandprovide

newlocalISIandMNPT.

Step 3Validation of Local ISI

• RunINRValidatewith

newlocalISIandMNPT

TheISIwebalgorithmwill

checkthatresultsarewithin

expectedvalues.

1.Pass:UselocalISIand

MNPT

2.Fail:CallILrepresentative

forassistance

uWith ISI Calibrate, INR Validate and ISIweb, total control of INR results is just a click away.

ISIweb

efficiency and Compliance through IsIweb

uAccessible from www.ilww.com and www.ilus.com homepages, the ISIweb online registration screen allows users to register and log in instantaneously.

uFollowing establishment of an ISIweb profile, all subsequent INR Validate and ISI Calibrate interactions will recall this data for maximum efficiency.

uISI Calibration Reports are generated online through ISIweb and can be stored electronically or printed, ensuring regulatory compliance.

werfen GroupWorldwide Locations

Corporate HeadquartersBarcelona,SpainTel.+34-93-4010101www.werfengroup.com

Instrumentation Laboratory HeadquartersBedford,MATel.+1-781-861-0710www.ilww.com

Us, Canada, Latin america and south america

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Pacific

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BeijingTel.+86-10-359006230

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Instrumentation Laboratory, Comesa and Izasa are companies of werfen Group.

Formoreinformation,visitwww.ilww.comorcontactyourlocalILsalesrepresentative/distributor.TheInstrumentationLaboratorylogo,HemosIL,ACL,ACLTOP,ISIwebandACLELITEaretrademarksofInstrumentationLaboratoryCompanyand/oroneofitssubsidiariesorparentcompanies,andmayberegisteredintheUnitedStatesPatentandTrademarkOfficeandinotherjurisdictions.Allotherproductnames,companynames,marks,logos,andsymbolsaretrademarksoftheirrespectiveowners.

©2009InstrumentationLaboratory.Allrightsreserved.

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References1. Poller L. International Normalized Ratios (INR): The first 20 years. JournalofThrombosisandHaemostasis, 2004: 849–860.2. Vanden Besselaar AMHP, Barrowcliffe TW, Houbouyan-Reveillard LL, Jesperson J, Johnston M, Poller L, Tripodi A. On Behalf of the Subcommittee

on Control of Anticoagulation of the Scientific and Standardization Committee of the ISTH, Guidelines on preparation, certification and use of certified plasmas for ISI calibration and INR determination. ThrombosisandHaemostasis,2004: 1946–1953.

3. Clinical and Laboratory Standards Institute/NCCLS. Procedures for Validation of INR and Local Calibration of PT/INR Systems; Approved Guideline. CLSI/NCCLS Document H54-A; Vol. 25 No. 23.

4. Ansell J, Hirsh J, Poller L, Bussey H, Hylek E. The pharmacology and management of the vitamin K antagonists: The seventh ACCP Conference on Anti thrombotic and Thrombolytic therapy.Chest,2004; 126 (3 suppl): 204S–233S.

5. Ginsberg JA, Crowther MA, White RH and Ortel TL. Anticoagulation Therapy. American Society of Hematology. Hematology, 20016. Hammelburger J, Bottenus R, Triscott M. Assignment and validation of INR Control can Calibrator Sets for Local calibration of INR, XXI ISTH,

Geneva, Switzerland July 6–12, 2007.7. Bottenus R, Hammelburger J, Triscott M. The Assignment and Use of INR Control and Calibrator Sets for Local Calibration of INR, ISLH 2007

Miami, Florida May 8–11, 2007.

Certified Plasmas for Local ISI Assignment and Validation

INR Validate 0020010500 3vialsx1mL(lyo) Level1 1.6–2.4 Level2 2.5–3.5 Level3 3.8–5.0

ISI Calibrate 0020010600 4vialsx1mL(lyo) LevelA 0.9–1.1 LevelB 1.6–2.4 LevelC 2.5–3.5 LevelD 3.8–5.0

PRodUCt PaRt NUmbeR KIt CoNFIGURatIoN LeVeLs oF aVK aPPRoxImate PLasma INR VaLUes*

* INR values are lot-specific. Please refer to product package inserts.Available for use on ACL TOP Family of Systems, ACL Advance, ACL ELITE/ELITE PRO, ACL 8/9/10000 and ACL Classic systems; and, with the following HemosIL reagents: RecombiPlastTin 2G, PT HS PLUS, PT Fib.