Ma rc ia L . Zuc ke r, Ph.D. ZIVD L L C 1 E xpla in the I - - PowerPoint PPT Presentation

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Ma rc ia L . Zuc ke r, Ph.D. ZIVD L L C

 E

xpla in the I NR, wha t it is, ho w it is c a lc ula te d a nd whe n it sho uld b e use d

 De sc rib e re a so na b le e xpe c ta tio ns fo r

I NR a g re e me nt a c ro ss pla tfo rms

 E

va lua te diffe re nt I NR syste ms to ma ximize sta nda rdize d pa tie nt c a re

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 Mo nito ring he mo sta sis

Bleeding Clotting

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Picture courtesy of Helena Laboratories

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Extrinsic Pathway Common Pathway CLOT X Xa II IIa (thrombin) WARFARIN LMWH & DXaI Hirudin & DTI Monitor with ACT / aPTT Monitor with PT Monitor with ???

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Drug Action Mechan- ism Moni- toring Effective Heparin Direct Inhibition of Thrombin AT cofactor APTT ACT Immediate Warfarin Decreases Production

• f factors

Vitamin K PT Delay 3-5 days

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 Ra t po iso n  Ca use o f “swe e t c lo ve r dise a se ”  Ora lly a c tive a ntic o a g ula nt

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 F

unc tio ns b y de c re a sing pro duc tio n o f Vita min K de pe nde nt c lo tting fa c to rs in live r

› De la ye d o nse t o f a ntic o a g ula tio n

 Po te nc y ma y va ry b y ma nufa c ture r  Do se re spo nse va rie s b y pa tie nt

› Die ta ry inte ra c tio ns › L ife -style influe nc e s

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Picture courtesy of Helena Laboratories

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 T

hro mb o pla stin iso la te d fro m:

› Diffe re nt spe c ie s

 pig ; c o w; huma n; e tc .

› Diffe re nt o rg a ns

 b ra in; thymus; lung ; e tc .  All yie ld diffe re nt re sults

› Re sults va ry b y instrume nt syste m in use

 Ma nua l tilt tub e “g o ld sta nda rd”  F

ib ro me te r; a uto ma te d c o a g ula tio n syste ms

 PT

ra tio s a do pte d to de te rmine the ra pe utic ra ng e

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 1977 – 1st I

RP de ve lo pe d

› Inte rna tio na l re fe re nc e thro mb o pla stin pre pa ra tio n

 1983 – K

irkwo o d de sc rib e s me tho d to c a lib ra te lo c a l thro mb o pla stin to I RP

› De fine re a g e nt ISI

 Inte rna tio na l se nsitivity inde x  1983 – WHO a nd I

ST H re c o mme nd the use

• f the I

NR to sta nda rdize PT re sult re po rting

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I

nte rna tio na l No rma lize d Ra tio (I NR)

› I SI = inte rna tio na l Se nsitivity I nde x

› INR ta rg e t ra ng e s a re spe c ifie d b y pa tie nt po pula tio ns, e .g .,

 DVT

, Afib , Atria l MHV: INR= 2.0 - 3.0

 Mitra l me c ha nic a l he a rt va lve : INR= 2.5 – 3.5  Individua l va ria tio n

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 I

SI

› Initia lly de te rmine d b y re a g e nt ma nufa c ture r › T ra c e a b le to IRP

 Inte rna tio na l Re fe re nc e thro mb o pla stin Pre pa ra tio n

› WHO de fine d pro c e ss

 Ca lib ra tio n up to INR = 4.5  ma nua l tilt tub e me tho d re fe re nc e

› L

• c a l c a lib ra tio ns c a n b e pe rfo rme d to de te rmine the

instrume nt spe c ific ISI

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 Me a n no rma l PT

› T he me a n no rma l PT sho uld b e de te rmine d fo r e a c h ne w b a tc h o f thro mb o pla stin with the sa me instrume nt use d to a ssa y the PT

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Antithrombotic therapy and prevention of thrombosis, 9th ed: ACCP guidelines. CHEST 2012; 141(2)(Suppl):e44S–e88S

 L

• c a l c a lib ra tio n ma y intro duc e va ria b ility

› Sa me sa mple yie lds diffe re nt re sults de pe nding

• n c a lib ra tio n me tho d

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ISI and MNPT from Poller et. al., J Thromb Haemost 2012; 10: 1379–84.

 Ma nufa c ture r a ssig ns I

SI a nd me a n no rma l PT (MNPT )

› L

• t spe c ific

 T

ra c e a b le to I RP

› Ofte n thro ug h se c o nda ry sta nda rd

 Ca nno t b e c ha ng e d b y e nd use r

› Do e s no t va ry b y lo c a tio n o f te sting

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b ut it WI L L Co rre la te

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 Po int o f Ca re

› Who le Blo o d › No Adde d Antic o a g ula nt › No Dilutio n › No Pre a na lytic a l De la y

 L

a b o ra to ry

› Pla te le t Po o r Pla sma › So dium Citra te Antic o a g ula nt › 1:9 Dilutio n › Va ria b le Pre a na lytic a l De la y > Re a g e nt > I nstrume nt > Clo t de te c tio n

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 L

a b Sa mple s

› Blo o d c o lle c tio n

 ve nipunc ture te c hniq ue

tub e und e rfill

 c itra te c o nc e ntra tio n he mo lysis

 3.2% sho uld b e use d

› T ra nspo rt

 te mpe ra ture e ffe c ts

 e xpo sure b e yo nd 18 - 24°C a ffe c ts re sult  c o ld te mpe ra ture s sig nific a ntly re d uc e PT

 sa mple c lo tting  d e la y in te sting

 va ria b le e ffe c ts d e pe nd ing o n a mb ie nt te mpe ra ture ,

c o nc o mita nt me d ic a tio ns a nd time o f d e la y

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CLSI documents H03; H21 and H54

 Po int o f Ca re

› Blo o d c o lle c tio n

 fing e rstic k te c hniq ue  use o f c a pilla ry tub e fo r tra nsfe r

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Co rre la tio n da ta fro m: Ple sc h e t. a l, T hro mb Re s 2008; 123:381–9

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T hr

• mboplastin

Analyze r c alibr ation T hr

• mboplastin

Analyze r c alibr ation

I nno vin CA1500 L

• c a l vs rT

F / 95 He pa to Quic k ST A-R Ma nufa c ture r Re c o mb ipla stin ML A1800 L

• c a l vs rT

F / 95 T hro mb o te st K C10 L

• c a l vs OBT

/ 79 Ne o pla stin Plus ST A-R Ma nufa c ture r T hro mb o pla stin C Plus CA1500 Ma nufa c ture r

 10 OAT

pa tie nts a c ro ss 7 a na lyze r/ re a g e nt c o mb ina tio ns



Mc Gla sso n, DL 2003: L a b Me d 34: 124 – 9.

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 36 pa tie nts o ve r 4 visits e a c h

› 3 POC; 1 la b



So lvik e t. a l., 2010: Clin Che m 56:1618–1626 (2010)

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INR % diff POC1-STA INR % diff POC 2-STA INR % diff POC 3-STA

Jacobson, J Thromb Thrombolysis (2008) 25:10–11

 Ob se rve d:

› + 0.4 a t INR = 2.0 › + 0.8 a t INR = 3.0 › + 1.2 a t INR = 4.0

 Sta nda rdiza tio n a s with g luc o se is unlike ly

› disc re te a na lyte to b e te ste d › ve rsus a b io lo g ic pro c e ss

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 Re sults Ava ila b le While Pa tie nt is Pre se nt

› Impro ve d Antic o a g ula tio n Ma na g e me nt

 Inc re a se d T

ime in T he ra pe utic Ra ng e

› Impro ve d Sta nda rd o f Ca re › Sta ff E ffic ie nc y

 I

mme dia te Re te sting (if ne e de d)

› F ing e rstic k Sa mpling

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Sourc e INR Range Agre e me nt L imits

CL SI POCT 14A 1.0 to 2.5 + 0.4 CL SI POCT 14A 2.6 to 3.5 + 0.7 L ite ra ture 3.6 to 5.0 + 0.9 L ite ra ture Ab o ve 5.0 + 1.2

 POCT

14A Co nse nsus Ca ndida te L imit

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Supportive Literature Citations Lassen JF et al. INR for PT in patients ……Critical difference and probability of significant change in consecutive measurements, Clin Chem. 1995. Oral Anticoagulation Monitoring Study Group. POC PT measurement for professional and patient self-testing use, Am J Clin Path. 2001. Hobbs et al. Is the INR reliable? A trial ……..in hospital laboratory and primary care settings. J Clin Pathol, 1999. Jacobson A. Warfarin monitoring: POC INR limitations and interpretations. J Thromb Thrombolysis, 2008. Ansell J et al. Pharmacology and management of Vit K: Am Coll Chest Physicians Evidence Based Clinical Practice

• Guidelines. CHEST 2008.

 L

• we r do se ?

 K

e e p sa me do se ?

 Ra ise Do se ?  T

e st Ag a in?

 T

e st mo re o fte n?

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60 80 100 Incidence per 100 Patient-Years

Hemorrhagic Reserve Thrombotic Reserve Increased Thrombotic Risk Increased Hemorrhagic Risk

Adapted from Cannegeiter, et. al. N Engl J Med 1995; 333:11-17

20 40

Thrombotic and Hemorrhagic Reserve for a Patient with a target INR of 3.0

target

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Goa l is to Ma inta in a T ig ht T he r a pe utic Ra ng e



Pra c tic a l Co nside ra tio ns

› A-F ib c o mp lic a tio ns inc re a se fro m 4% a t a g e 65 to >15% a t a g e 75

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• 1. Unde rsta nd limita tio ns in the I

NR

› Whe ne ve r a pa tie nt unde rg o e s duplic a te te sting o n diffe re nt syste ms, the re is the po te ntia l fo r disa g re e me nt

• 2. Atte mpt to ha ve pa tie nts ma na g e d

with a c o nsiste nt me tho do lo g y

Jacobson, J Thromb Thrombolysis (2008) 25:10–11

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 I

NR wa s de ve lo pe d to mo nito r e ffe c t o f vita min K a nta g o nists (wa rfa rin, o the rs)

 I

NR is ina ppro pria te sc a le fo r mo nito ring c o a g ulo pa thie s

 Mo st POC PT

/ I NR te sts c le a re d ONL Y fo r mo nito ring pa tie nts re c e iving o ra l a ntic o a g ula tio n the ra py suc h a s Co uma din o r wa rfa rin.

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 Mo nito ring he mo sta sis

Bleeding Clotting

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Marcia L. Zucker mlzucker.zivd@gmail.com