THROMBOELASTOGRAPHY FOR CARDIAC SURGEONS Andrew Ronald Consultant Cardiac Anaesthetist Aberdeen...

THROMBOELASTOGRAPHY FOR CARDIAC SURGEONS

Andrew RonaldConsultant Cardiac Anaesthetist

Aberdeen Royal Infirmary,Aberdeen, UK

[email protected]

THROMBOELASTOGRAPHY

•What is Thromboelastography?

•Where does it “fit into” our usual coagulation monitoring and what (if any) new information does it give us

•Why is it useful in Cardiac Surgery?

WHAT IS THROMBOELASTOGRAPHY

Functional Description

Thromboelastography monitors the thrombodynamic

properties of blood as it is induced to clot under a low

shear environment resembling sluggish venous flow. The

patterns of change in shear-elasticity enable the

determination of the kinetics of clot formation and growth

as well as the strength and stability of the formed clot.

The strength and stability of the clot provide information

about the ability of the clot to perform the work of

haemostasis, while the kinetics determine the adequacy

of quantitative factors available to clot formation

THROMBOELASTOGRAPHYSo what does it do?

•Clot formation

•Clot kinetics

•Clot strength & stability

•Clot resolution

THROMBOELASTOGRAPHYBasic Principles

• Heated (37C) oscillating cup

• Pin suspended from torsion wire into blood

• Development of fibrin strands “couple” motion of cup to pin

• “Coupling” directly proportional to clot strength

• tension in wire detected by EM transducer

THROMBOELASTOGRAPHYBasic Principles

• Electrical signal amplified to create TEG trace

• Result displayed graphically on pen & ink printer or computer screen

• Deflection of trace increases as clot strength increases & decreases as clot strength decreases

THROMBOELASTOGRAPHYRefinements to Technique

TEG accelerants / activators / modifiers• Celite / Kaolin / TF accelerates initial coagulation

• Reopro (abciximab) blocks platelet component of coagulation

• Platelet mapping reagents modify TEG to allow analysis of Aspirin / Clopidigrol effects

Heparinase cups• Reverse residual heparin in sample• Use of paired plain / heparinase cups allows

identification of inadequate heparin reversal or sample contamination

THROMBOELASTOGRAPHY

Where does the TEG fit into coagulation monitoring and

what new information does it give us?

COAGULATION MONITORINGWhat is coagulation?

COAGULATION MONITORINGConventional tests

Tests of coagulation• Platelets

• number• function

• Clotting studies• PT• APTT• TCT

• Fibrinogen levels

Tests of fibrinolysis• Degradation

products

The TEG gives us dynamic information on all aspects of

conventional coagulation monitoring

THROMBOELASTOGRAPHYSample display

THROMBOELASTOGRAPHYThe “r” time

r time•represents period of time of latency from start of test to initial fibrin formation

•in effect is main part of TEG’s representation of standard”clotting studies”

•normal range• 15 - 23 mins (native blood)• 5 - 7 mins (kaolin-

activated)

THROMBOELASTOGRAPHYWhat affects the “r” time?

r time by• Factor deficiency • Anti-coagulation• Severe

hypofibrinogenaemia

• Severe thrombocytopenia

r time by• Hypercoagulabil

ity syndromes

THROMBOELASTOGRAPHYThe “k” time

k time•represents time taken to achieve a certain level of clot strength (where r time = time zero ) - equates to amplitude 20 mm

•normal range• 5 - 10 mins (native blood)

• 1 - 3 mins (kaolin-

activated)

THROMBOELASTOGRAPHYWhat affects the “k” time?

k time by• Factor deficiency • Thrombocytopeni

a• Thrombocytopath

y• Hypofibrinogenae

mia

k time by• Hypercoagulabil

ity state

THROMBOELASTOGRAPHYThe “” angle

angle•Measures the rapidity of fibrin build-up and cross-linking (clot strengthening)•assesses rate of clot formation

•normal range• 22 - 38 (native blood)• 53 - 67(kaolin-

activated)

THROMBOELASTOGRAPHYWhat affects the “” angle?

Angle by• Hypercoagulabl

e state

Angle by• Hypofibrinogenem

ia• Thrombocytopeni

a

THROMBOELASTOGRAPHYThe “maximum amplitude” (MA)

Maximum amplitude •MA is a direct function of the maximum dynamic properties of fibrin and platelet bonding via GPIIb/IIIa and represents the ultimate strength of the fibrin clot

•Correlates to platelet function• 80% platelets• 20% fibrinogen

•normal range• 47 – 58 mm (native blood)• 59 - 68 mm (kaolin-activated)• > 12.5 mm (ReoPro-blood)

THROMBOELASTOGRAPHYWhat affects the “MA” ?

MA by• Hypercoagulabl

e state

MA by• Thrombocytopenia• Thrombocytopathy• Hypofibrinogenem

ia

THROMBOELASTOGRAPHYFibrinolysis

LY30•measures % decrease in amplitude 30 minutes post-MA

•gives measure of degree of fibrinolysis

•normal range• < 7.5% (native blood)• < 7.5% (celite-activated)

•LY60• 60 minute post-MA data

THROMBOELASTOGRAPHYOther measurements of

Fibrinolysis

A30 (A60)• amplitude at 30 (60) mins post-MA

EPL•earliest indicator of abnormal lysis

•represents “computer prediction” of 30 min lysis based on interrogation of actual rate of diminution of trace amplitude commencing 30 secs post-MA

•early EPL>LY30 (30 min EPL=LY30)•normal EPL < 15%

THROMBOELASTOGRAPHYWhat measurements are affected by

fibrinolysis?

Fibrinolysis leads to: LY30 / LY60 EPL A30 / A60

THROMBOELATOGRAPHYQuantitative analysis

• Clot formation– Clotting factors - r, k times

• Clot kinetics– Clotting factors - r, k times– Platelets - MA

• Clot strength / stability– Platelets - MA– Fibrinogen - Reopro-mod MA

• Clot resolution– Fibrinolysis - LY30/60; EPL A30/60

THROMBOELATOGRAPHYQualitative analysis

TEG v CONVENTIONAL STUDIES

Conventional tests• test various parts of coag

cascade, but in isolation• out of touch with current

thoughts on coagulation• plasma tests may not be

accurate reflection of what actually happens in patient

• difficult to assess platelet function

• static tests• take time to complete

best guess or delay treatment

TEG• global functional

assessment of coagulation / fibrinolysis

• more in touch with current coagulation concepts

• use actual cellular surfaces to monitor coagulation

• gives assessment of platelet function

• dynamic tests• rapid results rapid

monitoring of intervention

Advantages of TEG over conventional coagulation

monitoring

• It is dynamic, giving information on entire coagulation process, rather than on isolated part

• It gives information on areas which it is normally difficult to study easily – fibrinolysis and platelet function in particular

• Near-patient testing means results are rapid facilitating appropriate intervention

• It is cost effective compared to conventional tests

THROMBOELATOGRAPHYWhy might it have a role in Cardiac

Surgery?

Because patients bleed postoperatively

It is often difficult to identify exactly why they are bleeding

BLEEDING IS A PROBLEM IN IN CARDIAC SURGERY

• Why do patients bleed postoperatively?

• Can we do anything to prevent/minimize this blood loss

• How is the bleeding patient managed conventionally?

– what factors may force us to readdress this

• How can the TEG change the way we manage the bleeding patient?

• (Does use of the TEG improve patient care?)

WHY DO PATIENTS BLEED AFTER CARDIAC SURGERY?

• Preoperative & pre-CPB factors

• CPB factors

• Post-CPB factors

• Surgical Bleeding

POSTOPERATIVE BLEEDINGPreoperative / Pre-CPB factors

•Aspirin &/or Clopidigrol - anti-platelet effects

•Reopro - abciximab; anti GpIIb/IIIa agent

•Warfarin / Heparin anticoagulation

•Pre-existing clotting factor &/or platelet abnormalities

POSTOPERATIVE BLEEDINGCPB factors

•Decreased platelet count

•Heparin effect

•Alien contact

POSTOPERATIVE BLEEDINGPost-CPB factors

•Reversal of heparin

•Non-functional platelet

•Fibrinolysis

POSTOPERATIVE BLEEDINGSurgical factors

•Type of Surgery•complicated surgery• redo surgery

•Cardiac surgery can be bloody!•Big pipes, big holes, big vessels

• Blood and Surgery• Lung of pig, Pancreas of cow, Sperm of

salmon• Foreign surfaces & cellular trauma • Drug effects• Thrombin activation• Non-functional Platelets• Altered blood flow• Abnormal Coagulation & Fibrinolysis• Inflammatory response to CPB

WHY DO PATIENTS BLEED AFTER CARDIAC SURGERY?

HOW DO PATIENTS EVER CLOT AFTER CARDIAC SURGERY?

CAN WE DO ANYTHING TO PREVENT OR MINIMISE THIS

BLOOD LOSS?

• Stop Aspirin / Clopidigrol

• Use of anti-fibrinolytics

• “Cell-salvage” techniques

• Surgical technique

• Blood Component therapy

HOW DO CARDIAC SURGEONS TREAT POSTOPERATIVE

BLEEDING?

• More Stitches / Surgicell / topical haemostatic agents

• More Protamine • Tranexamic acid • Aprotinin /Aprotinin infusion• Platelets• FFP• “Coagulation factor crash packs”• Blood• More Protamine• More Platelets & FFP +/- Cryoprecipitate• Reopening (5% nationally; 3.5% in ARI)

PROBLEMS ASSOCIATED WITH BLOOD & BLOOD PRODUCT USAGE

IN CARDIAC SURGERY

• Drain on donor pool• supply v demand

• Financial consequences• direct and indirect

• Patient consequences• “Hazards of Transfusion”

• Infective / Immunogenic / Thrombogenic problems

• “Other” problems• Patients don’t want it

Can we rationalize usage of blood & blood products in Cardiac Surgery but still ensure the right patient gets the

right component he really needs at the right time

We need to move away from the

traditional “carpet bombing” of the coagulation system in the bleeding

postoperative cardiac surgical patient with all its associated risks towards a more “targeted” clinical therapeutic

approach?

Can we use the TEG to facilitate and support this change in the management of

the bleeding patient?

We know the problems

• Bloody surgery• Anticoagulants

• Abnormal platelet function

• Damaged / ineffective platelets

• Abnormal fibrinolysis

Can the TEG help us?• Clot formation

• Clotting factors

• Clot kinetics• Clotting factors• Platelets

• Clot strength & stability

• Platelets

• Clot resolution• Fibrinolysis

CLINICAL STUDIES OF TEG USE IN CARDIAC SURGERY

• Thromboelastography-guided transfusion algorithm reduces transfusions in complex cardiac surgery. Shore-Lesserson, Manspeizer HE, DePerio M et alAnesth Analg 1999; 88 : 312-9

• Reduced Hemostatic Factor Transfusion using Heparinase Modified TEG during Cardiopulmonary Bypass. von Kier S, Royston DBr J Anaesthesia 2001 ; 86 : 575-8

Thromboelastography-guided transfusion algorithm reduces transfusions in complex

cardiac surgery Shore-Lesserson et al, Anesth Analg 1999; 88 :

312-9• Prospective blinded RCT

• Patients randomized to either routine transfusion practice or TEG-guided transfusion therapy for post-cardiac surgery bleeding

• Inclusion surgery types• single / multiple valve replacement• combined CABG + valve surgery• cardiac reoperation• thoracic aortic surgery

• Standard anaesthetic / CPB management• routine use of EACA



312-9

• Surgeon / Anaesthetist “blinded” to group - TEG / coag results reviewed by independent investigator who then instructed clinicians what to give

• Data collection• Coagulation studies and TEG data appropriate to

each group• Multiple time point assessment of

• Transfusion requirements• FFP requirements• platelet transfusion requirements• Mediastinal tube drainage (MTD)



312-9

Routine transfusion groupCoagulation tests taken after Protamine administration used to direct transfusion therapy in presence of bleeding

Transfused when Hct <25% (<21% on CPB)



312-9

TEG-guided groupPlatelet count + Celite & TF-activated TEG’s with heparinase modification taken at rewarm on CPB (36C) - result used to order blood products from lab

TEG samples run after Protamine administration (celite & TF activated plus paired plain / heparinase cups) used to direct actual transfusion therapy (in the presence of bleeding)

Transfused when Hct <25% (<21% on CPB)



312-9

Routine transfusion group52 patients

31/52 (60%) received blood

16/52 (31%) received FFP

15/52 (29%) received Platelets

TEG-guided group53 patients

22/53 (42%) received blood(p=0.06)

4/53 (8%) received FFP(p=0.002)(p<0.04 for FFP volume)

7/53 (13%) received Platelets (p<0.05)

MTD no statistical difference

Reduced Hemostatic Factor Transfusion using Heparinase Modified TEG during Cardiopulmonary

Bypassvon Kier S, Royston D, Br J Anaesthesia 2001 ; 86 :

575-8

• Study design• 2 groups of 60 patients

• Group 1 - conventional v retrospective TEG-predicted therapy• Group 2 - prospective RCT - clinician-guided v TEG-guided

• Complex surgery• transplants• multiple valve / valve + revascularisation• multiple revascularisation with CPB > 100 mins

• Outcomes• FFP usage• Platelet usage• Mediastinal tube drainage (MTD)



575-8Group 1Microvascular bleeding managed conventionally using

standard coag tests• Microvascular bleeding

• Blood loss > 400ml in first hour• Blood loss > 100ml/hr for 4 consecutive hours

• Triggers to treat• PT & / or APTT ratio >1.5 x normal• Platelet count < 50,000 /dl• Fibrinogen concentration < 0.8 mg/dl• Patients who returned to theatre (3) “replaced” by

additional pts


Bypassvon Kier S, Royston D, Br J Anaesthesia 2001 ; 86 : 575-

8

Group 1Predicted transfusion requirements using TEG algorithm • Retrospective analysis of TEG data at PW (post-warm)

sample point



575-8

Group 1 - conventional therapy60 patients

22/60 given blood component therapy

Actual usage38 units FFP

17 units Platelets

Group 1 - TEG predicted therapy60 patients

7/60 predicted to need component therapy(p<0.05)

Predicted usage6 units FFP

2 units Platelets(p<0.05)



575-8

Group 2• Prospective RCT arm of study

• 60 patients randomly allocated to one of two groups• Clinician-directed therapy

• products given for bleeding as judged clinically by clinical team responsible for case

• TEG algorithm-directed therapy• products given for bleeding as directed by

TEG-driven protocol

• Patients who returned to theatre for bleeding (1 in each group) were “replaced” with additional patients



575-8

Sampling protocol • all celite-activated heparinase modified samples

• Baseline (BL)• Post-warm (PW)• Post-protamine (PP) + celite-activated plain sample

TEG treatment algorithmr>7 min but <10.5 min mild clotting factors 1 FFPr>10.5 min but <14 min mod clotting factors 2 FFP r>14min severe clotting factors 4 FFPMA<48mm mod in platelet no / function 1 platelet poolMA<40mm severe in platelet no / function 2 platelets

poolsLY30 >7.5% fibrinolysis Aprotinin



575-8

Group 2 - Clinician-directed30 patients

10/30 received blood component therapy

16 units FFP

9 units Platelets

12 hour MTD losses [median (lower & upper quartile)]390 (240, 820)

Group 2 - TEG directed30 patients

5/30 given blood component therapy(p<0.05)

5 units FFP

1 unit Platelets(p<0.05)

12 hour MTD losses [median (lower & upper quartile)]470 (295, 820)

(NS)

There appears to be good clinical evidence that TEG can guide

therapy and decrease our blood product usage

TEG studies - caveats

• studies looked at wide range of procedures & patient management - difficult to extrapolate study findings to all units

• considerable variability in pre-study management across units

• concomitant introduction of postoperative transfusion protocols at same time as TEG may cloud TEG outcomes

• variability in TEG-guided protocols and sources of derived data- what exactly is normal in post-cardiac surgery population?

• by its very nature use of TEG facilitates early intervention, whereas use of conventional tests delays intervention. Is this enough in itself to explain apparent differences?

THROMBOELASTOGRAPHY

How do I use it?

THROMBOELASTOGRAPHY IN PRACTICE

Sampling protocol • all kaolin-activated heparinase modified

samples– Baseline (BL)– Post-warm (PW)– Post-protamine (PP) + kaolin-activated

plain sample

– further paired CITU samples for bleeding if required

Is the patient bleeding?• Check samples running / already run = PW, PP, CITU • “Eyeballing” of trends

PP r-Plain > r-Heparinase Inadequate heparin reversal Protaminer>9-10 min clotting factors FFPMA<48mm platelet no / function PlateletsLY30 >7.5% (or EPL > 15%) Hyperfibrinolysis Antifibrinolytic

Still bleeding?• repeat TEG

• still abnormal further factors as indicated• normal consider surgical bleeding

Thromboelastography in practiceResidual Heparin

Thromboelastography in practiceLong r time - clotting factor deficiency

Thromboelastography in practiceLow MA - Platelet dysfunction

Thromboelastography in practiceFibrinolysis

THROMBOELASTOGRAPHYSummary

• Thromboelastography (TEG) provides near-patient, real-time, dynamic measurements of coagulation and fibrinolysis

• It is ideally designed to provide useful information amidst the cauldron of factors which contribute to post-cardiac surgical bleeding

• Use of TEG to drive post-cardiac surgery protocols for management of bleeding has been shown to be cost-effective and will decrease the patient’s exposure to blood and blood component therapy with its concomitant well-documented risks

• Appropriate use of TEG can result in genuine cost savings in Cardiac Surgery patients

Quand on ne sait pas, on a peur

When you don’t know, you are afraid

TEG=Clotting knowledge

THROMBOELASTOGRAPHY FOR CARDIAC SURGEONS Andrew Ronald Consultant Cardiac Anaesthetist Aberdeen...

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