Transcript Thromboelastography in Cardiac Surgery

THROMBOELASTOGRAPHY FOR
CARDIAC SURGEONS
Andrew Ronald
Consultant 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
THROMBOELASTOGRAPHY
So what does it do?
• Clot formation
• Clot kinetics
• Clot strength & stability
• Clot resolution
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 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
Where does the TEG fit into
coagulation monitoring and what
new information does it give us?
COAGULATION MONITORING
What is coagulation?
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
THROMBOELASTOGRAPHY
Sample display
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)
THROMBOELASTOGRAPHY
What affects the “r” time?
r time  by
• Factor deficiency
• Anti-coagulation
• Severe
hypofibrinogenaemia
• Severe
thrombocytopenia
r time  by
• Hypercoagulability
syndromes
THROMBOELASTOGRAPHY
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)
THROMBOELASTOGRAPHY
What affects the “k” time?
k time  by
• Factor deficiency
• Thrombocytopenia
• Thrombocytopathy
• Hypofibrinogenaemia
k time  by
• Hypercoagulability
state
THROMBOELASTOGRAPHY
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)
THROMBOELASTOGRAPHY
What affects the “” angle?
 Angle  by
• Hypercoagulable
state
 Angle  by
• Hypofibrinogenemia
• Thrombocytopenia
THROMBOELASTOGRAPHY
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)
THROMBOELASTOGRAPHY
What affects the “MA” ?
MA  by
• Hypercoagulable
state
MA  by
• Thrombocytopenia
• Thrombocytopathy
• Hypofibrinogenemia
THROMBOELASTOGRAPHY
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
THROMBOELASTOGRAPHY
Other measurements of Fibrinolysis
A30 (A60)
• amplitude at 30 (60) mins postMA
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%
THROMBOELASTOGRAPHY
What measurements are affected by fibrinolysis?
Fibrinolysis leads to:
•  LY30 /  LY60
•  EPL
•  A30 /  A60
THROMBOELATOGRAPHY
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
THROMBOELATOGRAPHY
Qualitative 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
THROMBOELATOGRAPHY
Why 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 BLEEDING
Preoperative / 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 BLEEDING
CPB factors
• Decreased platelet count
• Heparin effect
• Alien contact
POSTOPERATIVE BLEEDING
Post-CPB factors
• Reversal of heparin
• Non-functional platelet
• Fibrinolysis
POSTOPERATIVE BLEEDING
Surgical factors
• Type of Surgery
• complicated surgery
• redo surgery
• Cardiac surgery can be bloody!
• Big pipes, big holes, big vessels
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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
Can the TEG help us?
• Clot formation
• Clotting factors
• Clot kinetics
• Clotting factors
• Platelets
• Damaged / ineffective
platelets
• Clot strength &
stability
• Platelets
• Abnormal fibrinolysis
• 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
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
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)
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)
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 & TFactivated 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)
Thromboelastography-guided transfusion algorithm
reduces transfusions in complex cardiac surgery
Shore-Lesserson et al, Anesth Analg 1999; 88 : 312-9
Routine transfusion group
TEG-guided group
52 patients
53 patients
31/52 (60%) received blood
22/53 (42%) received blood
(p=0.06)
16/52 (31%) received FFP
4/53 (8%) received FFP
(p=0.002)
(p<0.04 for FFP volume)
15/52 (29%) received Platelets
7/53 (13%) received Platelets
(p<0.05)
MTD no statistical difference
Reduced Hemostatic Factor Transfusion using Heparinase
Modified TEG during Cardiopulmonary Bypass
von 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)
Reduced Hemostatic Factor Transfusion using Heparinase
Modified TEG during Cardiopulmonary Bypass
von 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 > 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 Bypass
von 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
Reduced Hemostatic Factor Transfusion using Heparinase
Modified TEG during Cardiopulmonary Bypass
von Kier S, Royston D, Br J Anaesthesia 2001 ; 86 :
575-8
Group 1 - conventional therapy
60 patients
Group 1 - TEG predicted therapy
60 patients
22/60 given blood component
therapy
7/60 predicted to need component
therapy
(p<0.05)
Actual usage
Predicted usage
38 units FFP
6 units FFP
17 units Platelets
2 units Platelets
(p<0.05)
Reduced Hemostatic Factor Transfusion using Heparinase
Modified TEG during Cardiopulmonary Bypass
von 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
Reduced Hemostatic Factor Transfusion using Heparinase
Modified TEG during Cardiopulmonary Bypass
von 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
r>7 min but <10.5 min
r>10.5 min but <14 min
r>14min
MA<48mm
MA<40mm
LY30 >7.5%
mild  clotting factors
mod  clotting factors
severe  clotting factors
mod  in platelet no / function
severe  in platelet no / function
 fibrinolysis
1 FFP
2 FFP
4 FFP
1 platelet pool
2 platelets pools
Aprotinin
Reduced Hemostatic Factor Transfusion using Heparinase
Modified TEG during Cardiopulmonary Bypass
von Kier S, Royston D, Br J Anaesthesia 2001 ; 86 : 575-8
Group 2 - Clinician-directed
30 patients
Group 2 - TEG directed
30 patients
10/30 received blood component
therapy
16 units FFP
5/30 given blood component
therapy
(p<0.05)
5 units FFP
9 units Platelets
1 unit Platelets
(p<0.05)
12 hour MTD losses
[median (lower & upper quartile)]
390 (240, 820)
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 datawhat 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 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 in practice
Residual Heparin
Thromboelastography in practice
Long r time - clotting factor deficiency
Thromboelastography in practice
Low MA - Platelet dysfunction
Thromboelastography in practice
Fibrinolysis
THROMBOELASTOGRAPHY
Summary
• Thromboelastography (TEG) provides near-patient, realtime, 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 costeffective and will decrease the patient’s exposure to blood
and blood component therapy with its concomitant welldocumented 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