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G.K.Kumar. 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?. THROMBOELASTOGRAPHY. TEG was developed by Hartert in 1948

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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?
THROMBOELASTOGRAPHY
thromboelastography functional description

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

THROMBOELASTOGRAPHY-Functional Description
thromboelastography so what does it do

Clot formation

  • Clot kinetics
  • Clot strength & stability
  • Clot resolution
THROMBOELASTOGRAPHY-So what does it do?
thromboelastography basic principles
THROMBOELASTOGRAPHY-Basic 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
thromboelastography basic principles1
THROMBOELASTOGRAPHY-Basic 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
thromboelastography refinements 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- Refinements to Technique
where does the teg fit into coagulation monitoring and what new information does it give us
Where does the TEG fit into

coagulation monitoring and what new information does it give us?

THROMBOELASTOGRAPHY

coagulation monitoring conventional tests
COAGULATION MONITORING-Conventional 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
The TEG gives us dynamic information on all aspects of conventional coagulation monitoring
thromboelastography the r time
THROMBOELASTOGRAPHY- The “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)
what affects the r time
What affects the “r” time?

r time  by

  • Factor deficiency
  • Anti-coagulation
  • Severe hypofibrinogenaemia
  • Severe thrombocytopenia

r time  by

  • Hypercoagulability syndromes
the k time
The “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)
what affects the k time
What affects the “k” time?

k time  by

  • Factor deficiency
  • Thrombocytopenia
  • Thrombocytopathy
  • Hypofibrinogenaemia

k time  by

  • Hypercoagulability state
the angle
The “” 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)
what affects the angle
What affects the “” angle?

 Angle  by

  • Hypercoagulable state

 Angle  by

  • Hypofibrinogenemia
  • Thrombocytopenia
the maximum amplitude ma
The “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)
what affects the ma
What affects the “MA” ?

MA  by

  • Hypercoagulable state

MA  by

  • Thrombocytopenia
  • Thrombocytopathy
  • Hypofibrinogenemia
fibrinolysis
Fibrinolysis

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
other measurements of fibrinolysis
Other 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%
what measurements are affected by fibrinolysis
What measurements are affected by fibrinolysis?

Fibrinolysis leads to:

  •  LY30 /  LY60
  •  EPL
  •  A30 /  A60
quantitative analysis
Quantitative 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

teg v conventional studies
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
Advantages of TEG over conventional coagulation monitoring
slide28
Because patients bleed postoperatively

It is often difficult to identify exactly why they are bleeding

THROMBOELATOGRAPHYWhy might it have a role in Surgery?

bleeding is a problem in 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?)
BLEEDING IS A PROBLEM IN SURGERY?
postoperative bleeding

Aspirin &/or Clopidigrol - anti-platelet effects

  • Reopro - abciximab; anti GpIIb/IIIa agent
  • Warfarin / Heparin anticoagulation
  • Pre-existing clotting factor &/or platelet abnormalities
POSTOPERATIVE BLEEDING

Preoperative / factors

postoperative bleeding1

Decreased platelet count

  • Heparin effect
  • Alien contact
POSTOPERATIVE BLEEDING

Intraop factors

postoperative bleeding2

Reversal of heparin

  • Non-functional platelet
  • Fibrinolysis
POSTOPERATIVE BLEEDING

Postop factors

postoperative bleeding surgical factors

Type of Surgery

    • complicated surgery
    • redo surgery
  • Cardiac surgery can be bloody!
    • Big pipes, big holes, big vessels
POSTOPERATIVE BLEEDINGSurgical factors
slide34

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

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
CAN WE DO ANYTHING TO PREVENT OR MINIMISE THIS BLOOD LOSS?
how do 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
HOW DO TREAT POSTOPERATIVE BLEEDING?
problems associated with blood blood product usage

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
PROBLEMS ASSOCIATED WITH BLOOD & BLOOD PRODUCT USAGE
slide40

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?

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

slide41

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 al

Anesth Analg 1999; 88 : 312-9

  • Reduced Hemostatic Factor Transfusion using Heparinase Modified TEG during Cardiopulmonary Bypass.

von Kier S, Royston D

Br J Anaesthesia 2001 ; 86 : 575-8

CLINICAL STUDIES OF TEG USE IN CARDIAC SURGERY
slide43

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

Thromboelastography-guided transfusion algorithm reduces transfusions in complex cardiac surgery Shore-Lesserson et al, Anesth Analg 1999; 88 : 312-9

slide44

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)

Thromboelastography-guided transfusion algorithm reduces transfusions in complex cardiac surgery Shore-Lesserson et al, Anesth Analg 1999; 88 : 312-9

slide45

Thromboelastography-guided transfusion algorithm reduces transfusions in complex cardiac surgery Shore-Lesserson et al, Anesth Analg 1999; 88 : 312-9

Routine transfusion group

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

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

slide46

Thromboelastography-guided transfusion algorithm reduces transfusions in complex cardiac surgery Shore-Lesserson et al, Anesth Analg 1999; 88 : 312-9

TEG-guided group

Platelet 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)

slide47

Thromboelastography-guided transfusion algorithm reduces transfusions in complex cardiac surgery Shore-Lesserson et al, Anesth Analg 1999; 88 : 312-9

Routine transfusion group

52 patients

31/52 (60%) received blood

16/52 (31%) received FFP

15/52 (29%) received Platelets

TEG-guided group

53 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

slide48

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)

Reduced Hemostatic Factor Transfusion using Heparinase Modified TEG during Cardiopulmonary Bypassvon Kier S, Royston D, Br J Anaesthesia 2001 ; 86 : 575-8

slide49

Group 1

Microvascular 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

Reduced Hemostatic Factor Transfusion using Heparinase Modified TEG during Cardiopulmonary Bypassvon Kier S, Royston D,Br J Anaesthesia 2001 ; 86 : 575-8

slide50

Group 1

Predicted transfusion requirements using TEG algorithm

  • Retrospective analysis of TEG data at PW (post-warm) sample point

Reduced Hemostatic Factor Transfusion using Heparinase Modified TEG during Cardiopulmonary Bypassvon Kier S, Royston D,Br J Anaesthesia 2001 ; 86 : 575-8

slide51

Reduced Hemostatic Factor Transfusion using Heparinase Modified TEG during Cardiopulmonary Bypassvon Kier S, Royston D,Br J Anaesthesia 2001 ; 86 : 575-8

Group 1 - conventional therapy

60 patients

22/60 given blood component therapy

Actual usage

38 units FFP

17 units Platelets

Group 1 - TEG predicted therapy

60 patients

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

Predicted usage

6 units FFP

2 units Platelets

(p<0.05)

slide52

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

Reduced Hemostatic Factor Transfusion using Heparinase Modified TEG during Cardiopulmonary Bypassvon Kier S, Royston D,Br J Anaesthesia 2001 ; 86 : 575-8

slide53

Sampling protocol

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

TEG treatment algorithm

r>7 min but <10.5 min mild  clotting factors 1 FFP

r>10.5 min but <14 min mod  clotting factors 2 FFP

r>14min severe  clotting factors 4 FFP

MA<48mm mod  in platelet no / function 1 platelet pool

MA<40mm severe  in platelet no / function 2 platelets pools

LY30 >7.5%  fibrinolysis Aprotinin

Reduced Hemostatic Factor Transfusion using Heparinase Modified TEG during Cardiopulmonary Bypassvon Kier S, Royston D,Br J Anaesthesia 2001 ; 86 : 575-8

slide54

Reduced Hemostatic Factor Transfusion using Heparinase Modified TEG during Cardiopulmonary Bypassvon Kier S, Royston D,Br J Anaesthesia 2001 ; 86 : 575-8

Group 2 - Clinician-directed

30 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 directed

30 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)

slide55

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?
TEG studies - caveats
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
THROMBOELASTOGRAPHY IN PRACTICE
slide59

Is the patient bleeding?

  • Check samples running / already run = PW, PP, CITU
  • “Eyeballing” of trends

PP r-Plain > r-Heparinase Inadequate heparin reversal Protamine

r>9-10 min  clotting factors FFP

MA<48mm  platelet no / function Platelets

LY30 >7.5% (or EPL > 15%) Hyperfibrinolysis Antifibrinolytic

Still bleeding?

  • repeat TEG
    • still abnormal  further factors as indicated
    • normal  consider surgical bleeding
thromboelastography summary

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
THROMBOELASTOGRAPHYSummary