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

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

1

 E

xpla in why ACT s fro m diffe re nt syste ms a re no t the sa me

 De ve lo p a pla n fo r switc hing fro m o ne

ACT syste m to a no the r

 De sc rib e why ACT

a nd a PT T a re no t inte rc ha ng e a b le

2

 Mo difie d L

e e -White c lo tting time

 Add b lo o d to g la ss tub e , sha ke

 Pla c e in he a t b lo c k  Visua l c lo t d e te c tio n

 F

irst de sc rib e d in 1966 b y Ha tte rsle y

› Ac tiva te d Clo tting T ime

 Add b lo o d to g la ss tub e with dirt, sha ke

 Dia to ma c e o us e a rth a c tiva to r  Pla c e in he a t b lo c k  Visua l c lo t d e te c tio n

 Pro po se d fo r b o th sc re e ning fo r c o a g ula tio n

de fe c ts a nd fo r he pa rin mo nito ring

3

 Gluc o po lysa c c ha ride  MW ra ng e : 6,000 - 25,000 da lto ns  Only ~1/ 3 mo le c ule s a c tive › Must c o nta in spe c ific se q ue nc e o f g luc o sa c c ha ride s to func tio n

Heparin + AT Heparin + AT Heparin + AT Heparin + AT Heparin Activity Prekallikrein ….. Kallikrein D-dimers FDP Fibrinolysis 12 11 9 8 10 5 2 7 Fibrinogen CLOT (Fibrin)

Modified from Utley, Vol.1, 1982

T hro mb in

 Po te nc y va rie s b y ma nufa c ture r

› Po te nc y va rie s b y lo t

 Do se re spo nse va rie s b y pa tie nt

› Ha lf life ra ng e s fro m 60 - 120 minute s › No n-spe c ific b inding

 F

unc tio ns b y a c c e le ra ting a c tio n o f a ntithro mb in

› Antithro mb in le ve l c ritic a l fo r a ppro pria te re spo nse

 Mo nito ring he mo sta sis fo r he pa rin

a ntic o a g ula te d pa tie nts

Bleeding Clotting

7

 Po int o f Ca re

› Imme dia te turn a ro und › Ra pidly a djust a ntic o a g ula nt do sing a s ne e de d

 He pa rin – ha lf life va rie s b y pa tie nt

 Do se re q uire d va rie s b y pa tie nt  Po te nc y va rie s b y lo t

 Dire c t thro mb in inhib ito rs – ve ry sho rt ha lf life

 Re q uire imme d ia te inte rve ntio n  No a ntid o te a va ila b le

 Ca rdia c surg e ry  Pe rc uta ne o us c o ro na ry inte rve ntio n (PCI

)

 I

nte rve ntio na l c a rdio lo g y

 E

CMO

 Critic a l c a re  I

nte rve ntio na l ra dio lo g y

 E

le c tro physio lo g y

 Va sc ula r surg e ry  e tc .

 I

ndustry Sta nda rd Sinc e 1970s

 Re c o mme nde d a s 1o me tho d in AmSE

CT g uide line s

 ACT

impro ve s o utc o me in CPB, PCI

› AACC NACB L MPG fo r POCT

 Stro ng ly re c o mme nd ACT

mo nito ring o f he pa rin a ntic o a g ula tio n a nd ne utra liza tio n in c a rd ia c surg e ry.

(Cla ss A, L e ve l I)

› Insuffic ie nt e vide nc e to re c o mme nd spe c ific ta rg e t time s fo r use during c a rdio va sc ula r surg e ry. (Cla ss I – c o nflic ting e vide nc e a c ro ss c linic a l tria ls).  E

a sy to run

10

 Disa dva nta g e s

› E a c h syste m yie lds diffe re nt numb e rs › Mo st se nsitive to hypo the rmia a nd he mo dilutio n › L ittle o r no c o rre la tio n to he pa rin le ve l

 e spe c ia lly true fo r pe dia tric pa tie nts  “Sta nda rd” ta rg e t time = 480 se c o nds

› De ve lo pe d with ma nua l ACT › Sug g e ste d due to hig h va ria b ility

11

 Dia g no stic

› Ca the te riza tio n

 lo c a te a nd ma p ve sse l b lo c ka g e (s)  de te rmine ne e d fo r inte rve ntio na l pro c e dure s

› E le c tro physio lo g y

 I

nte rve ntio na l

› Ba llo o n a ng io pla sty › Athe re c to my (ro to -ro o te r) › Ste nt pla c e me nt

12

 Ang io pla sty, Athe re c to my, Ste nt pla c e me nt › 10,000 unit b o lus do se o r 2 - 2.5 mg / kg › ta rg e t ACT 300 - 350 se c o nds › T a rg e t time b e re duc e d if Re o Pro Use d  Re o Pro is o ne o f 3 “GPII

b / I I I a ” Inhib ito rs

 Ca the te riza tio n a nd E

le c tro physio lo g y

› Sa me do sing a nd ta rg e ts fo r va sc ula r surg e ry

› 2500 - 5000 unit b o lus do se › fre q ue ntly no t mo nito re d › if mo nito re d – T

a rg e ts ~ 200 se c o nds OR twic e b a se line

 E

xtra Co rpo re a l Me mb ra ne Oxyg e na tio n

› Ve ry sma ll windo w o f sa fe ty › NACB Guide line s:

 Stro ng ly re c o mme nd ACT

mo nito ring to c o ntro l he pa rin a ntic o a g ula tio n during E

• CMO. (Cla ss A –

L e ve l II I )

 T

a rg e t time s fo r E CMO b a se d o n the ACT syste m.

(Cla ss B – L e ve l II I )

› T a rg e t o fte n 180 – 200 se c o nds

 Ba se d o n He mo c hro n P214/ 215 tub e s

 De te rmine whe n to pull the fe mo ra l she a th › Pre ma ture she a th pull c a n le a d to b le e ding . › De la ye d re mo va l c a n inc re a se time in CCU. › T a rg e t se t a t e a c h site .

 ACT

ta rg e ts ra ng e fro m 150 – 220 se c o nd s

 a PT

T ta rg e ts ra ng e fro m 40 – 70 se c o nd s

 Mo nito r he pa rin the ra py › T a rg e t time s de te rmine d b y e a c h fa c ility › ACT

• r a PT

T

15

 ACT

› Ac tiva te d c lo tting time › POC Only › L

• w, mo de ra te o r

hig h do se he pa rin

 Syste m de pe nde nt

a PT

T

› Ac tiva te d pa rtia l

thro mb o pla stin time

› L

a b o ra to ry o r POC

› L

• w do se he pa rin o nly
• Syste m de pe nde nt

uppe r limit

 Why a re the re sults fro m diffe re nt syste ms

SO VE RY diffe re nt?

› Multiple a c tiva to rs › Multiple de te c tio n me c ha nisms › NO sta nda rdiza tio n

 ACT

Diffe re nc e s

 1969 -

HE MOCHRONOME T E R

› Ha tte rsle y ACT

 Auto ma te d he a ting  Ob je c tive fib rin c lo t

d e te c tio n

› two diffe re nt a c tiva to rs

 CA510 (la te r F

T CA510)

 d ia to ma c e o us e a rth

 P214 g la ss b e a d

100 200 300 400 500 600 700 1 2 3 4 5 Heparin (units/ml) Clotting Time (sec)

C-ACT P214

ECMO Dialysis CATH PTCA CPB

 He mo T

e c ACT

(la te r Me dtro nic s ACT Plus) › Add b lo o d to dua l c a rtridg e

 L

iq uid ka o lin a c tiva to r

 F

la g mo ve s up a nd do wn

 As fib rin fo rms, mo tio n slo ws  Instrume nt displa ys c lo tting

time

475 500 525 550 575 600 625 650 675 700

Pre CPB 15 min 30 min 45 min 60 min 75 min 90 min 105 min

Seconds

Hemochron Hemotec

differences ignored by clinicians

 Re po rte d in lite ra ture >20 ye a rs

› Clinic a l e va lua tio ns o f He mo c hro n - mid 1970’ s › By 1981 –

 po o r c o rre la tio n b e twe e n ACT

a nd he pa rin le ve l

› By 1988

 He mo c hro n a nd He mo T

e c c linic a lly diffe re nt

 E

a rly ’ 80’ s to Pre se nt

› Impro ve d c linic a l o utc o me with ACT use

 NACB L

a b o ra to ry me dic ine pra c tic e g uide line fo r po int o f c a re c o a g ula tio n te sting 2007

 http:/ / www.a a c c .o rg / Site Co lle c tio nDo c ume nts/ NACB/ L

MP G/ POCT / Cha pte r%204.pd f

 Mic ro sa mple ACT

s - He mo c hro n Jr

› Add b lo o d to sa mple we ll, pre ss sta rt

 Silic a , ka o lin a nd pho spho lipid (ACT

+)

 Dia to ma c e o us e a rth (ACT

• L

R)

 Sa mple pumpe d a c ro ss re stric tio n  F

lo w slo ws with c lo t fo rma tio n

 Optic s me a sure mo tio n  Clo tting time displa ye d

50 150 250 350 450 550 50 100 150 200 250 300 350 400 450 500 FTCA510 ACT

• Jr. ACT

ACT+ ACT-LR FTCA510

 Ab b o tt - i-ST

AT

› Add b lo o d to c a rtridg e , pre ss sta rt

 Dia to ma c e o us e a rth o r ka o lin

› Inse rt into instrume nt › No c lo t de te c tio n

 Synthe tic thro mb in sub stra te  E

le c tro -a c tive c o mpo und fo rme d a nd de te c te d a mpe ro me tric a lly

 “Clo tting time ” re po rte d

26

100 200 300 400 500 600 700 800 900 1000 200 400 600 800 1000 1200

Compar ator ACT HE MOCHRON 1 ACT He moc hron 2 i- ST AT Ce lite i- ST AT Kaolin

 E

va lua te b y c linic a l a g re e me nt

› Sta nda rd split sa mple c o rre la tio n › Sa mple s a c ro ss e ntire ra ng e › Co rre la tio n c o e ffic ie nt

 R > 0.88

› T wo b y T wo ta b le o f a g re e me nt

27

28

y = 1.09x - 7.53 R = 0.915 100 200 300 400 500 600 700 800 900 200 400 600 800 Ne w ACT Curre nt ACT

 CVOR e xa mple

Curre nt Ne w N %

> 480 > 520 72 34% > 480 < 520 19 9% < 480 > 520 7 3% <480 <520 117 54%

 88% a g re e me nt

• 21 o f 26 disc re pa nc ie s
• Curre nt va lue within 10% o f 480
• 5 o f 26 disc re pa nc ie s
• Ne w le a ds to a dditio na l he pa rin g ive n

 Da ta use d to pre dic t ne w ta rg e t time  Clinic a l a g re e me nt de te rmine d fro m

pre dic te d ta rg e t time

 Only me tho d o f va lue in E

CMO, she a th pull

› Ra ng e o f va lue s to o sma ll fo r c o rre la tio n a na lysis

29

 Dire c t thro mb in inhib ito rs (DT

I s)

› Use d if pa tie nt a t risk fo r HIT

 He pa rin induc e d thro mb o c yto pe nia  “He pa rin a lle rg y”

› Arg a tro b a n › Ang io ma x

 No ACT

F DA c le a re d fo r mo nito ring DT I s

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

31

 Arg a tro b a n › Synthe tic a na lo g o f L

• a rg inine

 Re ve rsib le b ind ing to thro mb in

› PCI mo nito ring : ACT 300 – 450

 Pa pe rs sta te sta nd a rd ACT

ta rg e ts fo r CPB

 Ang io ma x › Synthe tic a na lo g hirudin (b iva lirudin)

 Re ve rsib le b ind ing to thro mb in

› L a b e ling re q uire s ACT a fte r initia l b o lus

 Orig ina l studie s with He mo c hro n ACT

• L

R

 Any ACT

>250 se c

 ACT

s a re Glo b a l Assa ys

› Use d to mo nito r he pa rin

 He pa rin is no n-ho mo g e no us  Diffe re nc e b y ma nufa c ture r & L

• t

 ACT

s diffe r:

› By ma nufa c ture r › By a c tiva to r › By de te c tio n me c ha nism

 Must e sta b lish c linic a l e q uiva le nc e

› Ne w ta rg e t time s tha t re fle c t c linic a l pra c tic e

33