G.K.Kumar

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?

TEG was developed by Hartert in 1948

Thromboelastogradphy originally monitors the

thrombodynamic properties of blood as it is induced to clot

under a low shear environment resembling sluggish venous

flow.

This 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

Clot formation

Clot kinetics

Clot strength & stability

Clot resolution

• 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

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

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

Where does the TEG fit into coagulation monitoring and what new information does it give us?

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

r timerepresents 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)

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

hypofibrinogenaemia

• Severe thrombocytopenia

r time by• Hypercoagulability

syndromes

k timerepresents 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)

k time by• Factor deficiency • Thrombocytopeni

a• Thrombocytopath

y• Hypofibrinogenae

mia

k time by• Hypercoagulabil

ity state

angleMeasures 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)

Angle by• Hypercoagulabl

e state

Angle by• Hypofibrinogenem

ia• Thrombocytopeni

a

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)

MA by• Hypercoagulabl

e state

MA by• Thrombocytopenia• Thrombocytopathy• Hypofibrinogenem

ia

LY30measures % 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

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

EPLearliest 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%

Fibrinolysis leads to: LY30 / LY60 EPL A30 / A60

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

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

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

Because patients bleed postoperatively

It is often difficult to identify exactly why they are bleeding

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?)

Aspirin &/or Clopidigrol - anti-platelet effects

Reopro - abciximab; anti GpIIb/IIIa agent

Warfarin / Heparin anticoagulation

Pre-existing clotting factor &/or platelet abnormalities

Preoperative / factors

Decreased platelet count

Heparin effect

Alien contact

Intraop factors

Reversal of heparin

Non-functional platelet

Fibrinolysis

Postop 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

• Stop Aspirin / Clopidigrol

• Use of anti-fibrinolytics

• “Cell-salvage” techniques

• Surgical technique

• Blood Component therapy

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

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

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

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

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

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)

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

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

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)

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

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)

Group 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

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

point

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)

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

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

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

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?

How do I use it?

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 (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