Systemic heparinization during peripheral vascular surgery: Thromboelastographic, activated coagulation time, and heparin titration monitoring

Systemic Heparinization Dwing Peripheral Vascular Surgery: Thromboelastographic, Activated Coagulation Time, and Heparin Titration Monitoring P. Martin, PhD, D. Greenstein, ME BS, N.K. Gupta, MCh, D.R. Walker, Fifteen patients (9 male, 6 female) undergoing peripheral vascular surgery were monitored during surgery for evidente of subclinical anticoagulation using the activated coagulation time (ACT), thromboelastography (TEG), and heparin titration monitoring. Assessments were made at 30-minute intervals before and after the occlusion clamp. Mean (?SD) ACT values preoperatively were 111 (17) seconds, and 10 minutes after 5,000 IU of heparin, the ACT was 264 (57) seconds (P < 0.001). Intraoperatively, there was a significant decline in ACT values at 30 minutes (ACT 228 [50] sec, P < 0.005) and 60 minutes (200 [46] sec, P < 0.001) postheparin. NO significant differente in ACT was observed between samples drawn distally and proximally to the clamp. TEG

A

PPROPRIATE

hcparinization

surgery rcmains

a dilemma.

not a bolus injcction

agulation artcrial

of heparin

to prcvcnt clamp.

vascular

provides adequate

thrombosis

’3 Morcovcr.

in periphcral

It is unclear whethcr distal

or

antico-

to an occluding

in the abscncc

of clinically

significant oozing from thc surgical tield, heparin ncutralization is commonly

avoidcd at thc termination

dure. Thc activatcd coagulation

time (ACT)”

valuablc

high-dosc

means of monitoring

of the procchas bccome a

heparin

during cardiac surgery with cardiopulmonary in addition. (TEG)

this group

has found

thromboclastography

to bc a useful adjunct to conventional

monitoring

following

activity

bypass,‘.” and

cardiopulmonary

bypass.’ Thc TEG

KEY WORDS: anticoagulation, thromboelastography

6X.2 kg. Standard operative All patients minute\

may provide insight into how appro-

priately hcparin is inhibiting Thc

coagulation

aims of thc present

asscss whethcr

This

intraoperatively.

study were

thc empirical

thrcefold:

(1)

to

dosage of S.Oo0 IU of heparin

routincly givcn to all patients provides adequate

anticoagu-

of intravenoub Bucks. IJK)

the application

was administered

thc clamp from an artcrial

catheter

monitoring.

Accurately

The

after

arterial

occlusion.

IO that of an cmpirical providc an objective

IV bolus (5,000 IU)

approach

dosc: and (3) to

mcans of intraopcrativcly

monitoring

Graft

NO clamp

rcmained

temperature

patencg

was

on for more

was maintained

assessed

ACT

assesscd

the

activatcd

by surfacc

detection

of clot (Iibrin)

‘Timer (Hemotcc in cach

clotting

contact.

time

Thc

of iresh

end-point

formation.

(‘0)

duplicate

durinp

cartridge

kaolin-activatcd

desccnt. This i\ detcctcd

clectivc

reconstructivc

aorta-distal

hypabs surgery lor aorta-iliac and 0 patients

underwent

(9 male.

6 femalc)

undergoing

surgery (h patients

underwent

occlusive disease [Dacron Y-graft]

femoro-distal

bypass grafting

[PTFE])

were studied. The agrs of thr patients ranged from 47 to 82 years.

Grove.

Channel.

I.eeds IS14

ótiQ. G~gbnd.

clotting

impedes thc rate ol

on a Thromboelastograph

;cnd processctl

within

2 hours.

whole

hy thc torxion uirc.

D (Haemo-

bloed

This

involved

the

into a disposable of l.29’?

w/v

Once thr clot began 10 farm.

librin strands gradually strcngthened

thc

their held on the cup and pin.

‘l‘hc cup is coupled to the pin. and the elasticity of thc bloed clot is to the pin and is recorded on the thermal paper. of whole

blood

using ;m automated

f IMS (Hemotcc asay

to quantitatc

te,t

usus

Inc.

heparin

concentration

protaminc Englewood,

titration CO).”

rhe conccntration

of hcparin

cartridgc

Channel contains a different

constant

amount

of thromhoplastin neutralixs

the

In brief.

the

VascularAnesthes~a,

titration

in rhe sample.

Each

amount of protaminc with a to nctivate

the tesl.

The

the heparin is the tirst toclot.

‘l‘he end point of thc ICSI i\ dctection of clou formalicm.

JournalofCardmthoraacand

was also

system,

thc principle of hepariniprotaminc

Channel that most clo~ly

150

plungcr

and thoroughly mixed and activated hy raising and lowering thc pin suxpendcd

hrparin

York Rd,

Thc

sample, but the tihrin

isotonic C‘aCl: were thcn addcd to the cup (lo recalcify thc sample)

Hepcon

f fqitai,

hy

mechanism contained

1L). In brief, whole bloed was collected

of 0.3tl ml. of citrated

performed

Surgery. Killin&ck

C‘oagulafion

by a phot~>-~Iptical system located in the

Thc TEC; was performed

Assessment

.~ddrrss corwspondence IO 1’. !Mortin. Principul Rewurch Sctenrrsr.

bloed

cover asbemhly of thc instrument.

transmitted

Depurtmenr of Curdiorhorucic

wholc

dctects clot formation

plastic oscillating cup kept at 37°C‘. Sixty microlitcrs patients

using

of thc test is the

Thc Automated

Inc. Englewood.

disposable

pipctting

MATERIAL AND METHODS consccutive

at greater

postoperatively

measuring the ratr of fall of thc plunper-tlag

;~nd citratcd

Fifteen

and

than 90

Row ultrasound.

scope Inc. Morton

hcparin anticoagulation.

and at subse-

intervals until thc anastomosis was complete

Intraoperativc

33°C.

by

coagulation

timed samples were taken prior to heparin

5 minutes

the clamp> rclcased. minutes.

5

cross-

and below the cross-clamp

web formed

or metabolismi

arterial

needle from thc femoral vein for serial intraopcrative administration.

(porcine

only where the surgeon judged

paticnt variability

in sensitivity to hcparin

heparin

Whole hlood (H mL) was taken above

assemhly falls rapidly through an unclotted

of hcparin ncccssitatcs an altcrnativc

surgery,

as a bolus injection

of thc occluding

lation during artcrial cross-clamping; (2) to establish whether climination

vascular

techniques were used in all procedures.

S.lXH) IU

hcmostasis to bc inadequate.

Dopplcr

dynamic measurcment

bcfore

clamp. Protaminc

formation

to clot rctraction.

rcceived

mucosa, I.eo Lahb. Aylcsbury.

than

fibrinogenesis

heparin,

with u mcan of h7.S years. Lkxly mass ranged from 40 to Xh kg. mean

allows viscoelastic asscssment of thrombokinasc/thrombin through

MD

profiles were abolished in all patients immediately following heparinization. However, in 2 patients nearly complete return of the TEG coagulation profile was observed prior to the termination of the procedure and was associated with ACT values less than 160 seconds. The heparin device was unable to accurately monitor heparin elimination at these low doses. Variability of patient response to hepariniration necesritates the use of intraoperative monitoring of anticoagulation during peripheral vascular surgery. Copyright < 1994 by W.8. Saunders Company

quent 30-minutc

coagulation

FRCS, and R.C. Kester,

which ih

Vol 8, NO 2 (April), 1994: pp 150-152

HEPARIN MONITORING

151

DURING VASCULAR SURGERY

assessed by measuring the rate of fall of the plunger mechanism

contained in each cartridge Channel. This is detected hy a photooptica1 system located in the actuator assemhly of the instrument. The limit of detection IU!mL

(0.3

(sensitivity)

mg heparin!kg)

of this system for heparin

hased on currently

is 0.4

available

car-

tridges. AH parametrically (-cSD).

distributed

(:orrelation

(‘orrelation

variahles

are recorded

as mean

was assesscd using the Spearman

test (Oxstat.

Rank Sum

Wight Scientific. Londen). RESULTS

Only one paticnt

rcccivcd protamine

excessive periopcrativc before

and aftcr

shown in Tablc 10 minutes seconds.

heparin

administration in ACT

1. Variability

post-injcction

and

postopcrativcly

for

blccding. The rcsults of ACTvalues

showed

was marked;

mean

no correlation

heparin given per killigram

(5,000

IU)

are

response to hcparin at with

138 i thc

55.X

were

unahle

Hcpcon

to accurately

(0.4 IUlmL)

HMS

monitor

signiticant differente

dcvicc.

the authors

heparin

climination

post-heparin

injection

were at or bclow the limit of detection

of the device. However, rcduction

after initial

the ACT

with time following

prolongation bctween ACT

heparin

(Fig 2). Thcrc mcasurements

showcd a injcction

was no significant made proximal and

distal to the occlusion clamp. Thromboclastographic ment of anticoagulation inconsistent identified complete

pattern. in two

return

by TEG

patients of TEG

as cxemplilicd indices

(Table

monitoring

paticnt.

hy thc

throughout

near valucs

2). In addition, idcntified

In thc remain-

suggestcd that anticoagu-

surgcry was adequate

tcntly abolishcd)

(TEG

thc procedure.

profile

consis-

Thc return of

Table 1. Activated Coagulation Times Preheparin and 10 Minutes Portheparin Administration Patlelll NO

Preoperawe ACT

(N = 15 patients)

Postheparin

ProlongalIon ofACT

1

122

325

204

117

260

143 64

3

102

166

4

100

240

140

5

122

209

07

6

114

224

110

7

148

210

62

8

136

278

142

9

120

191

71

10

104

219

115

11

106

327

221

12

82

285

203

13

108

308

200

14

91

203

112

92

120

150

body weight)

Fig 1. Lack of conelation betwsen ACT meaaured 10 min poct-lVheparin administratfon and the units of heparin adminiatered per killigram body weight.

blood coagulability with ACT patient

293

identitied return),

was detccted

paticnt

by the TEG

values of less than

with partial

outcome

with

was associated

160 sec ( <200

although

sec in the

no adverse clinical

in any of these three patients.

an ACT

exhibited opcrative

value

greater

return of a TEG

than

200

NO

seconds

profile.

DISCUSSION

The tindings of the present nature

of anticoagulation

study confirm

induced

dose of heparin.z.3,v However, dcmonstrated by returning ated with Hcmotec

ACT

profiles)

in addition,

bolus

this study has

activity (as exemplified

in the operativc

values less than

period associ-

160 scconds (using the

timer). This tinding is ncw.

thcre is no consensus in the literature

ing anticoagulant

rcquiremcnts

plications

vascular

nonsurgical

thc vdriable

by an empirical

ex-vivo procoagulant TEG

ACT

Currcntly,

lIJ/mL ACTlOmin

2

15

Heparin Administercd (IVIKg

an was

to preoperativc

was present in one further during

anticoagulation

of return of blood coagulability

ing 12 paticnts. TEG lation

90

assess-

status during surgery revealed Inappropriatc

during the period of cross-clamping carly indications

60

30

body wcight (r = 0.14, P > 0.6,

from the blood; cven at 5 minutes the measurements

00

dose of

Fig 1). Using thc Hcmotcc

:

2

during

patients

of hcparin

surgcty.

suggest that

was cffcctive

3M)r.-

__ _.

regard-

to prevent thrombotic Studies

com-

pcrfonned

a rangc

in

of 0.2 to 0.5

in preventing

progression

.__.~

50

‘^0

5

10

IS

20

25

30

35

40

45

50

55

1

60

1

65

201

70

bfmw*~-

Mean (%SD) 110 (17)

249 151)

138 (56)

Fig 2. Change in ACT with time following heparin ?? dminiatration meesured proximal and distal to the occluding arterial clamp.

152

MARTIN ET AL

Table 2. Change in TEG Profile and ACT With Time in Patients Exhibiting Intraoperative

crcascd

Return Almost to Baseline (N = 2) _._

carly

P.311ent

platclct-librinogcn

postopcrativc

Thc rcsull of ACT

NO

Indices

4

Preoperatwe

30 Min

60 Min

8.0

17.5

10.0

R(min) K(min)

5.9

MA(mm)

59

ACT (sec)

100

8

monitoring

agulation

status rclativc

differcncc

10.0

was at variancc with that of C_Gglcy ct dccrcascd

220

158

6.2

13.5

6.0

3.8

21.5

3.0

49

36

54

136

205

157

partial

encc in APTT explaincd. that

who idcntilied

al.”

thromboplastin

in thc distal circulation.

vducs

in antico-

to sampling sitc. This ohscrvation

45

activatcd

with

proximal and distal IO thc

occlusion clamp rcvcalcd no apparent

19.0

K(min) ACT (sec)

W;I\ a~sociatccl

cv~nts.

32

R(min) MA(mm)

intcr:tction

thrombotic

timc (APTT)

Thc rcasons for thc ditfer-

ahovc and bclow thc aortic clamp wcrc not

although

increascd

it has heen suggestcd by Sobcl ct

thrombin

gcncration

is localizcd

;llti

10 thc

ischemic limb. NOTE. TEG parameters: thrombokinase

R = indicative of time for thrombin and

formation; K = indicative of time for fibrin formation

(fibrine-genesis); MA 7 indicative of clot strength: fibrin-platelet interaction (maximal amplitude).

of a thrombotic encountered

proccss. l” However,

cascade potentially

the operativc

formation. evidente

trauma of thc

leading to a highcr require-

ment for the blood heparin concentration

to prevcnt fibrin

Porte et al” suggcstcd that a hcparin leve1 of 0.7

to 1.0 IU/mL

may bc closer to actual rcquirements

of complete

tion in patients

inhibition

during

of fibrinopeptide

hemodialysis

undcr

citing

A gencra-

these condi-

tions.‘? Bloed lcvels of hcparin activity in thc present study (where measurable) use of Hepcon provided

were below this range. The speculative

HMS

littlc

technology

if any additional

in thc present information,

setting

although

in

defense of the instrument,

it should be pointed out that its

devclopment

specifically for cardiopulmonary

was targetcd

bypass monitoring

involving

significantly

greater

systemic

In a previous

study of paticnts

undcrgoing

vascular surgery, Tuman

et al13 reported

first

hypercoagulability

postopcrative

control patients undergoing and

furthermore

concluded

that

TEG

must bc monitored. measurc

administration.

of thc

and TEG.

hcparin

Icvcl.

thc clotting

hcparin.

Both

formcd

in the

to providc More

rcsponsc

opcrating

room

have

anticoagulation

TEG

no complications

cnsued).

and ACT

anticoagulation.

of

inadequate

bc

to suggest

may assist in provid-

This group recommcnds

that ACT valucs (using the Hcmotec period

per-

tcchnical

it scems rcasonablc

ing stcady-state

should

minimal

suggestivc

using TEG

200 scconds

may bc rcadily

with

of less than 200 scconds (and

that monitoring

than

thcy

that only thrce paticnts wcrc

profiles

with an ACT

an indirect

signiticantly.

to a givcn dosc of

of these tcchniques

support. While acknowledging to

To placc heparin

Thc present study uscd two complcmcn-

the ACT

dcmonstratcd

found

or

on a rational scientific basis, anticoagulation

tary mcthods.

ACT

timer) ofgrcatcr

maintained

throughout

in order to inhibit potential

thc

intraopcrativc

ACKNOWLEDGMENT

to

procedures,

cvidencc

for hcparin

administration

predictablc

with thc current empiri-

and

comparcd

noncardiovascular

to maintain

coagulopathy.

pcripheral

preoperativc

of patient response to heparin obscrvcd in

Icvcls of anticoagulation

operative

heparinization.x

day

adcquatc

cal formula

during surgery may lcad to activation

coagulation

The variability

this study makes it impossiblc

of

in-

The authors wish to acknowledge Killingbeck

Children’s

the genereus

support of the

Heart Surgery Fund during this study.

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