Transcript THROMBOELASTOGRAPHY G.K.Kumar

THROMBOELASTOGRAPHY
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-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-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?
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)
WHAT AFFECTS THE “R” TIME?
r time  by
•
•
•
•
Factor deficiency
Anti-coagulation
Severe
hypofibrinogenaemia
Severe
thrombocytopenia
r time  by
•
Hypercoagulability
syndromes
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?
k time  by
• Factor deficiency
• Thrombocytopenia
• Thrombocytopathy
• Hypofibrinogenaemia
k time  by
• Hypercoagulability
state
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?
 Angle  by
• Hypercoagulable
state
 Angle  by
• Hypofibrinogenemia
• Thrombocytopenia
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” ?
MA  by
• Hypercoagulable
state
MA  by
• Thrombocytopenia
• Thrombocytopathy
• Hypofibrinogenemia
FIBRINOLYSIS
LY30
measures
% decrease in
amplitude 30 minutes post-MA
gives
measure of degree of
fibrinolysis
normal
•
•
LY60
•
range
< 7.5% (native blood)
< 7.5% (celite-activated)
60 minute post-MA data
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 postMA
early
EPL>LY30 (30 min EPL=LY30)
normal EPL < 15%
WHAT MEASUREMENTS ARE AFFECTED BY
FIBRINOLYSIS?
Fibrinolysis leads to:
•  LY30 /  LY60
•  EPL
•  A30 /  A60
QUANTITATIVE ANALYSIS

Clot formation


Clot kinetics



Clotting factors - r, k times
Platelets - MA
Clot strength / stability



Clotting factors - r, k times
Platelets - MA
Fibrinogen - Reopro-mod MA
Clot resolution

Fibrinolysis - LY30/60; EPL
A30/60
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 SURGERY?
Because patients bleed postoperatively
It is often difficult to identify exactly why
they are bleeding
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?)
POSTOPERATIVE BLEEDING
Preoperative / factors
 Aspirin
&/or Clopidigrol - anti-platelet
 Reopro
- abciximab; anti GpIIb/IIIa agent
effects
 Warfarin
/ Heparin anticoagulation
 Pre-existing
clotting factor &/or platelet
abnormalities
POSTOPERATIVE BLEEDING
Intraop factors
 Decreased
 Heparin
 Alien
platelet count
effect
contact
POSTOPERATIVE BLEEDING
Postop factors
 Reversal
of heparin
 Non-functional
 Fibrinolysis
platelet
POSTOPERATIVE BLEEDING
SURGICAL 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
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 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
PROBLEMS ASSOCIATED WITH BLOOD & BLOOD
PRODUCT USAGE
 Drain
•
on donor pool
supply v demand
 Financial
•
direct and indirect
 Patient
•
consequences
“Hazards of Transfusion”
•
•
•
consequences
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
Can the TEG help us?
•
Clot formation
 Clotting factors
•
Clot kinetics
 Clotting factors
 Platelets
•
Clot strength &
stability
 Platelets
•
Clot resolution
 Fibrinolysis
Abnormal platelet
function
Damaged / ineffective
platelets
Abnormal 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 TEGguided 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 & 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)
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
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)
52 patients
53 patients
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
38 units FFP
Predicted usage
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 TEGdriven 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
12 hour MTD losses
[median (lower & upper quartile)]
390 (240, 820)
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 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, 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