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
Prekallikrein ….. Kallikrein 12 11 Heparin + AT Fibrinolysis 9 Heparin + AT 7 8 10 Heparin + AT 5 T hro mb in 2 Heparin + AT CLOT Fibrinogen (Fibrin) Heparin Activity Modified from Utley, Vol.1, 1982 D-dimers FDP
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 1 o 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 o r a PT T 15
a PT ACT T › Ac tiva te d pa rtia l › Ac tiva te d c lo tting thro mb o pla stin time time › L a b o ra to ry o r POC › POC Only › L o w do se he pa rin o nly › L o w, mo de ra te o r hig h do se he pa rin • Syste m de pe nde nt uppe r limit Syste m de pe nde nt
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
700 600 C-ACT Clotting Time (sec) 500 P214 400 300 200 CATH 100 PTCA CPB ECMO 0 Dialysis 0 1 2 3 4 5 Heparin (units/ml)
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
700 675 650 625 Seconds 600 575 Hemochron 550 525 Hemotec 500 475 Pre 15 30 45 60 75 90 105 CPB min min min min min min min 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
550 ACT+ 450 ACT-LR Jr. ACT FTCA510 350 250 150 50 50 100 150 200 250 300 350 400 450 500 FTCA510 ACT
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
1000 900 800 700 ACT 600 ator 500 Compar 400 300 He moc hron 2 200 i- ST AT Ce lite i- ST AT Kaolin 100 0 0 200 400 600 800 1000 1200 HE MOCHRON 1 ACT 26
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
900 CVOR e xa mple y = 1.09x - 7.53 800 R = 0.915 700 600 Ne w ACT 500 Curre nt Ne w N % 400 > 480 > 520 72 34% 300 200 > 480 < 520 19 9% 100 < 480 > 520 7 3% 0 0 200 400 600 800 <480 <520 117 54% Curre nt ACT 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 • 28
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 Monitor Monitor with with PT WARFARIN ACT / aPTT X Xa LMWH & DXaI Common Pathway Monitor II IIa (thrombin) with ??? Hirudin & DTI CLOT 31
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