THROMBOELASTOGRAPHY

1
THROMBOELASTOGRAPHY

• G.K.Kumar

2
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?

3
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

4
THROMBOELASTOGRAPHY-So what does it do?

• Clot formation
• Clot kinetics
• Clot strength stability
• Clot resolution

5
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

6
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

7
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

8
THROMBOELASTOGRAPHY

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

9
What is coagulation?
10
COAGULATION MONITORING-Conventional tests

• Tests of coagulation
• Platelets
• number
• function
• Clotting studies
• PT
• APTT
• TCT
• Fibrinogen levels

• Tests of fibrinolysis
• Degradation products

11

• The TEG gives us dynamic information on all
  aspects of conventional coagulation monitoring

12
THROMBOELASTOGRAPHY - Sample display
13
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 TEGs representation
  of standardclotting studies
• normal range
• 15 - 23 mins (native blood)
• 5 - 7 mins (kaolin-activated)

14
What affects the r time?

• r time ? by
• Factor deficiency
• Anti-coagulation
• Severe hypofibrinogenaemia
• Severe thrombocytopenia
• r time ? by
• Hypercoagulability syndromes

15
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)

16
What affects the k time?

• k time ? by
• Factor deficiency
• Thrombocytopenia
• Thrombocytopathy
• Hypofibrinogenaemia

• k time ? by
• Hypercoagulability state

17
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)

18
What affects the ? angle?

• ? Angle ? by
• Hypercoagulable state

• ? Angle ? by
• Hypofibrinogenemia
• Thrombocytopenia

19
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)
• gt 12.5 mm (ReoPro-blood)

20
What affects the MA ?

• MA ? by
• Hypercoagulable state

• MA ? by
• Thrombocytopenia
• Thrombocytopathy
• Hypofibrinogenemia

21
Fibrinolysis

• LY30
• measures decrease in amplitude 30 minutes
  post-MA
• gives measure of degree of fibrinolysis
• normal range
• lt 7.5 (native blood)
• lt 7.5 (celite-activated)
• LY60
• 60 minute post-MA data

22
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 EPLgtLY30 (30 min EPLLY30)
• normal EPL lt 15

23
What measurements are affected by fibrinolysis?

• Fibrinolysis leads to
• ? LY30 / ? LY60
• ? EPL
• ? A30 / ? A60

24
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

25
Qualitative analysis
26
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

27
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

28
THROMBOELATOGRAPHYWhy might it have a role in
Surgery?

• Because patients bleed postoperatively
• It is often difficult to identify exactly why
  they are bleeding

29
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?)

30
POSTOPERATIVE BLEEDING
Preoperative / factors

• Aspirin /or Clopidigrol - anti-platelet effects
• Reopro - abciximab anti GpIIb/IIIa agent
• Warfarin / Heparin anticoagulation
• Pre-existing clotting factor /or platelet
  abnormalities

31
POSTOPERATIVE BLEEDING
Intraop factors

• Decreased platelet count
• Heparin effect
• Alien contact

32
POSTOPERATIVE BLEEDING
Postop factors

• Reversal of heparin
• Non-functional platelet
• Fibrinolysis

33
POSTOPERATIVE BLEEDINGSurgical factors

• Type of Surgery
• complicated surgery
• redo surgery
• Cardiac surgery can be bloody!
• Big pipes, big holes, big vessels

34

• 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

35
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

36
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

37
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 dont want it

38
(No Transcript)
39
(No Transcript)
40
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?

41

• 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

42
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

43
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

44
Thromboelastography-guided transfusion algorithm
reduces transfusions in complex cardiac surgery
Shore-Lesserson et al, Anesth Analg 1999 88
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)

45
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 lt25 (lt21 on CPB)

46
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 TEGs 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 lt25 (lt21 on CPB)

47
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
• (p0.06)
• 4/53 (8) received FFP
• (p0.002)
• (plt0.04 for FFP volume)
• 7/53 (13) received Platelets
• (plt0.05)
• MTD no statistical difference

48
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 gt 100 mins
• Outcomes
• FFP usage
• Platelet usage
• Mediastinal tube drainage (MTD)

49
Reduced Hemostatic Factor Transfusion using
Heparinase Modified TEG during Cardiopulmonary
Bypassvon Kier S, Royston D, Br J Anaesthesia
2001 86 575-8

• Group 1
• Microvascular bleeding managed conventionally
  using standard coag tests
• Microvascular bleeding
• Blood loss gt 400ml in first hour
• Blood loss gt 100ml/hr for 4 consecutive hours
• Triggers to treat
• PT / or APTT ratio gt1.5 x normal
• Platelet count lt 50,000 /dl
• Fibrinogen concentration lt 0.8 mg/dl
• Patients who returned to theatre (3) replaced
  by additional pts

50
Reduced Hemostatic Factor Transfusion using
Heparinase Modified TEG during Cardiopulmonary
Bypassvon Kier S, Royston D, Br J Anaesthesia
2001 86 575-8

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

51
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 (plt0.05)
• Predicted usage
• 6 units FFP
• 2 units Platelets
• (plt0.05)

52
Reduced Hemostatic Factor Transfusion using
Heparinase Modified TEG during Cardiopulmonary
Bypassvon Kier S, Royston D, Br J Anaesthesia
2001 86 575-8

• 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

53
Reduced Hemostatic Factor Transfusion using
Heparinase Modified TEG during Cardiopulmonary
Bypassvon Kier S, Royston D, Br J Anaesthesia
2001 86 575-8

• Sampling protocol
• all celite-activated heparinase modified samples
• Baseline (BL)
• Post-warm (PW)
• Post-protamine (PP) celite-activated plain
  sample
• TEG treatment algorithm
• rgt7 min but lt10.5 min mild ? clotting factors
  1 FFP
• rgt10.5 min but lt14 min mod ? clotting factors
  2 FFP
• rgt14min severe ? clotting factors 4 FFP
• MAlt48mm mod ? in platelet no / function 1
  platelet pool
• MAlt40mm severe ? in platelet no / function 2
  platelets pools
• LY30 gt7.5 ? fibrinolysis Aprotinin

54
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 (plt0.05)
• 5 units FFP
• 1 unit Platelets
• (plt0.05)
• 12 hour MTD losses
• median (lower upper quartile)
• 470 (295, 820)
• (NS)

55

• There appears to be good clinical evidence that
  TEG can guide therapy and decrease our blood
  product usage

56
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?

57
THROMBOELASTOGRAPHY

• How do I use it?

58
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

59

• Is the patient bleeding?
• Check samples running / already run PW, PP,
  CITU
• Eyeballing of trends
• PP r-Plain gt r-Heparinase Inadequate heparin
  reversal Protamine
• rgt9-10 min ? clotting factors FFP
• MAlt48mm ? platelet no / function
  Platelets
• LY30 gt7.5 (or EPL gt 15) Hyperfibrinolysis
  Antifibrinolytic
• Still bleeding?
• repeat TEG
• still abnormal ? further factors as indicated
• normal ? consider surgical bleeding

60
Thromboelastography in practiceResidual Heparin
61
Thromboelastography in practiceLong r time -
clotting factor deficiency
62
Thromboelastography in practiceLow MA - Platelet
dysfunction
63
Thromboelastography in practiceFibrinolysis
64
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
  patients 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