Transcript Clinical Utility of Thromboelastography (TEG)

Clinical Utility of Thromboelastography
(TEG)
Lowell Chambers, MD
Secondary Hemostasis (Coagulation Cascade)
CLASSIC COAGULATION CASCADE
INTRINSIC PATH (PTT)
XII
EXTRENSIC PATH (PT)
XIIa
XI
XIa
IX
VIIa + TF
IXa + VIIIa
X
Xa + Va
Ca++
Prothrombin (II)
Fibrinogen (I)
Thrombin (IIa)
Fibrin (Ia)
Secondary Hemostasis (Coagulation Cascade)
PHYSIOLOGIC PATHWAY
VIII
VII +
IX
Platelet
Thrombin
TF
IXa
+
VIIIa*
V
X
XI
XIa
Xa
II
+
Va
XIII (transglutaminase)
Thrombin
Ca++
Fibrinogen
Fibrin
XIIIa
CrossLinked*
Fibrin
Cell-Based Hemostasis
Challenges in Coagulation Evaluation
• Evaluation of Platelet Function
• Monitoring of New generation anticoagulants
• Determination of Hyperfibrinolytic States
Coagulopathy of Trauma
Hyperfibrinolysis
Prot. C Activation
ACIDOSIS
Impaired Clotting Factor Function
Impaired Platelet Function
HYPOTHERMIA
HIGH ISS
HYPOTENSION
CNS Injuries
Increased
TF Release
Long Bone
Fxs
Fat Embolism
Increased
IVF & PRBCs
Dilution of Clotting
Factors & Platelets
DIC
C
O
A
G
U
L
O
P
A
T
H
Y
Hess J,… Hoyt D, … Bouillon B. J Trauma 2008; 65:748-54
Coagulopathy of Trauma
• ¼ Significant Trauma patients
• 4x increased mortality
• Multifactorial
• Currently addressed with:
- Whole
Blood
- 1:1:1 Massive Transfusion Protocols
Hess J,… Hoyt D, … Bouillon B. J Trauma 2008; 65:748-54
Coagulopathy of Trauma
• ¼ Significant Trauma patients
• 4x increased mortality
• Multifactorial
• Currently addressed with:
- Whole
Blood
- 1:1:1 Protocols
Improved
Outcomes
Hess J,… Hoyt D, … Bouillon B. J Trauma 2008; 65:748-54
Consequences of Overtransfusion
• Waste
• ALI / MSOF
• Thrombosis
Hyperfibrinolysis in Trauma
• See in 2-34% of Trauma Pts
• Increased risk with increased ISS, need
for transfusion, etc…
• Associated with increased mortality
Napolitano L,… Moore EE. J Trauma Acute Care Surg 2013; 74:1575-86
Fibrinolyis in Trauma
Kashuk J, Moore EE, et al. Ann Surg 2010; 252:434-44
Hyperfibrinolysis in Trauma
Napolitano L,… Moore EE. J Trauma Acute Care Surg 2013; 74:1575-86
• Randomized, multicenter trial (Europe, Asia, Africa)
• 20,127 trauma pts in 274 hospitals
• Inclusion criteria:
-Hemorrhagic Shock (SBP < 90, HR > 110)
-High risk of substantial bleeding
-Within 8 hr of injury
• TA (1gm over 10 min. then another gm over 8hr) versus Placebo
Tranexamic Acid in Trauma
All cause mortality reduction of 1.5%.
Lancet 2010; 376:23-32
Tranexamic Acid in Trauma
Lancet 2010; 376:23-32
All cause mortality reduction of 1.5% with TXA.
+
No harm from TXA
+
Low Cost (~$6.00/gm)
Potential to save 70-100,000
lives annually world-wide
(NNT1 = 67)
TXA in Trauma
• Cheap
• Safe
• Effective
SO WHY NOT USE ROUTINELY IN BLEEDING TRAUMAS ?
Added to WHO “Essential Medications List” in 2011
Napolitano L,… Moore EE. J Trauma Acute Care Surg 2013; 74:1575-86
CRASH-2 Problems
Napolitano L,… Moore EE. J Trauma Acute Care Surg 2013; 74:1575-86
Deficiencies in Current Coag. Assessment of
Severely Injured Trauma Pts
• No rapid, reliable assessment of hyperfibrinolysis
• Incomplete assessment of Coagulopathy of Trauma
- Lack of Qualitative Platelet Evaluation
- Lack of rapid Coag. Assessment
- Inability to assess when switch from hypo to hypercoagulable occurs
Thrombelastography (TEG)
• A viscoelastic point of care hemostatic assay
• Provides a graphic presentation of clot formation & lysis
Johansson PI, et al. Scan J Trauma, Resus, & Emerg Med 2009; 17:45.
Hemostasis Monitoring with the
TEG® System
Measures entire clotting process
Measures: ∆Clot strength / time
• Rate of clot formation
• Strength of clot
• Stability of clot

Hemostatic
status
TEG - History
• Initial description in 1948 (H Hartert)
Hartert H. Klin Wochenschr 1948; 26:577-83
• Important role in development of open heart surgery
and liver transplantation
Dr. Kurt von Koulla
& Hartert TEG
1950s Dr. Henry Swan &
Hypothermic Open Heart Procedures
1960s Dr. Thomas Starzl &
Liver Transplantation
TEG Method
• 0.36 ml whole blood incubated @ 37oC in a heated, kaolin-containing cup
(after being collected in Citrate – if delay in running > 3 min)
• Pin is suspended into cup and connected to a detector system (torsion wire)
• Cup is oscillated at an angle to the pin
• Fibrin forms between the cup and pin
• Formation of fibrin results in transmitted rotation from the cup to the pin
• Tracing is generated as a result of pin’s movement
• Pattern & duration of different aspects of tracing provides information on the
clotting and lysis process
TEG Tracing and Clotting Process
Maximum clot forms
Clot grows
Clot degradation
takes over
Platelet plug forms
Fibrin strands form
Clot dissolved
Damage repaired
Initiation
Time
 Continuous monitoring of
clotting process
 Generates parameters
that relate to each phase
Time (min)
Copyright © 2009 Haemonetics Corp.
Analytical Software
Graphical Representation
Kinetics
of clot
development
LY30
Percent lysis
30 minutes
after MA
Reaction time,
first significant
clot formation
Achievement
of certain clot
firmness
Maximum amplitude –
maximum strength of
clot
Copyright © 2009 Haemonetics Corp.
TEG Parameters: R
Reaction time
(4 – 8 min)
FFP
rVIIa
PCC
FFP +
Platelets
LMWH
LMWH +
ASA
Copyright © 2009 Haemonetics Corp.
TEG Parameters: K and angle ()
: Angle (47 - 74°)
Rate of clot growth
K: Clot kinetics (0 - 4 min)
Parameter
Clot time
Clot rate
Hemostatic
Activity
Fibrin mesh
IIa generation
Fibrin formation Fibrinplatelet
Hemostatic
Component
Coagulation Coag pathways
platelets
pathways

R
Dysfunction
Hypocoagulable
Hypercoagulable
4-8 min
K
 R (min)
 K (min)
 (deg)
 R (min)
 K (min)
 (deg)
FFP
Cryoprecipitate
Copyright © 2009 Haemonetics Corp.
TEG Parameters: MA
Maximum clot strength
Parameter
Clot time
Clot rate
Maximum clot strength
Hemostatic
Activity
Fibrin X-linking
IIa generation
Fibrin formation Fibrinplatelet
Platelet – fibrin interactions
Hemostatic
Component
Coagulation Coag pathways
platelets
pathways
Platelets (~80%)
Fibrin (~20%)
Maximum amplitude
(54 – 72 mm)
Platelets

MA
R
K
Dysfunction
Hypocoagulable
Hypercoagulable
 R (min)
 K (min)
 (deg)
 MA
 R (min)
 K (min)
 (deg)
 MA
Copyright © 2009 Haemonetics Corp.
ASA
TEG Parameters: LY30
Clot Breakdown
Parameter
Clot time
Clot rate
Lysis at 30 minutes
(0 – 7.5%)
Maximum clot strength
Clot stability
Hemostatic
Activity
Fibrin X-linking
IIa generation
Fibrin formation Fibrinplatelet
Platelet – fibrin(ogen) interactions
Reduction in clot strength
Hemostatic
Component
Coagulation Coag pathways
platelets
pathways
Platelets (~80%)
Fibrin(ogen (~20%)
Fibrinolysis
30 min
LY30

MA
TXA
ACA
R
EPL
K
Dysfunction
Hypocoagulable
Hypercoagulable
 R (min)
 K (min)
 (deg)
 MA
LY30 > 7.5%
EPL > 15%
 R (min)
 K (min)
 (deg)
 MA
N/A
Copyright © 2009 Haemonetics Corp.
TEG: Basic Patterns
Copyright © 2009 Haemonetics Corp.
Hemostasis Monitoring with the TEG®
System
Measures entire clotting process
Measures: ∆Clot strength / time
• Rate of clot formation
• Strength of clot
• Stability of clot

Copyright © 2009 Haemonetics Corp.
Hemostatic
status
Clinical Experience with standard TEG
• Majority of experience is with Cardiac & Liver Surgery
• > 20 clinical studies with > 4500 pts in last 25 years
• Varying quality (3 rand. clin. trials)
• Uniform findings of superiority of TEG over
routine coagulation tests.
Johansson PI, et al. Scan J Trauma Resus Emerg Med. 2009; 17:45
Standard TEG in Massive Tranfusion
• European Prospective Trial
• n=832 massively bleeding pts (21% trauma)
• TEG-guided patients:
- 20%
VS 32% mortality
- > FFP
- > Plts
Johansson PI, et al. Vax Sang 2009; 96:111-8
TEG in Trauma
Johansson PI, et al. Scan J Trauma Resus Emerg Med. 2009; 17:45
TEG in Trauma
• Differentiates different etiologies of the Coagulopathy
of Trauma
• Quicker & more accurate than coags.
• Permits ID of Hyperfibrinolysis
• Differentiates hyper VS hypocoagulability
• Gives info. on coag status with newer
anticoag. agents
Johansson PI, et al. Scan J Trauma Resus Emerg Med. 2009; 17:45
RapidTEG
• Tissue Factor added to Kaolin in cup
• Cuts processing time by ~ 50%:
- r-TEG
19.2 min to completion
- TEG 29.9 min
“
- Coags 34.1 min
“
Software available facilitating viewing of TEG on monitor in ICU/OR
real-time so initial information available within minutes.
Jeger V, et al. J Trauma 2009; 66:1253-7
Holcomb JB, et al. Ann Surg 2012; 256:476-86
r-TEG Tracing Comparison
RapidTEG
Standard
TEG
Differences: R range: 0-1 min
& use ACT
U Colorado Experience
More “Goal Directed” Therapy
“LEAN” Goals met c
blood products needed
Kashuk JL, Moore EE, et al. Transfusion 2012; 52:23-33
U Colorado Case Study
• 38 yo F auto VS ped. patient
• HD unstable from intra-abd bleeding
• Emergent Trauma Lap.
Initial r-TEG in OR
- PRBCs for hemorrhagic shock
- FFP for prolonged ACT
- Platelets for depressed MA
- 5 gm EACA for elevated LY30
U Colorado Case Study
• Intra-abd. Bleeding controlled but still “oozey”
2nd r-TEG in OR
- Improved coagulopathy (improved ACT)
- Improved platelet function (improved MA)
- Persistent Fibrinolysis (Sign. Increased LY30 still)
Additional EACA administered
U Colorado Case Study
• Pt continued to stabilize
• “Oozing” resolved
3rd r-TEG in OR
Ann Surg 2012; 256:476
r-TEG U Texas Experience
…
Holcomb JB, et al. Ann Surg 2012; 256:476
U Texas Approach
• Unstable Pt: 1:1:1 Transfusion
• Once surgical hemostasis achieved:
Holcomb JB, et al. Ann Surg 2012; 256:476
Baylor Approach
• ~ 10 year experience with TEG-directed resusc.
• Use conventional TEG rather than r-TEG
Tapia NM, … Mattox KL, Suliburk J. J Trauma Acute Care Surg 2013; 74: 378-86
Baylor Experience
• In October 2009 instituted 1:1:1 MTP
• Reviewed outcomes 21 months before & after
• Compared outcomes with TEG-directed VS
reflexive 1:1:1 MTP
Tapia NM, … Mattox KL, Suliburk J. J Trauma Acute Care Surg 2013; 74: 378-86
Baylor Experience
Tapia NM, … Mattox KL, Suliburk J. J Trauma Acute Care Surg 2013; 74: 378-86
Baylor Experience
• No improved survival in MTP with increased FFP utilization
• Some subsets of MTP with worse outcomes
Tapia NM, … Mattox KL, Suliburk J. J Trauma Acute Care Surg 2013; 74: 378-86
Baylor Approach
Tapia NM, … Mattox KL, Suliburk J. J Trauma Acute Care Surg 2013; 74: 378-86
? Mt Carmel Approach
> 3.0% TXA
Tapia NM, … Mattox KL, Suliburk J. J Trauma Acute Care Surg 2013; 74: 378-86
U Texas Approach
Holcomb JB, et al. Ann Surg 2012; 256:476
TEG & PE risk assessment
• Prospective Study with 2,070 consecutive Cat. 1 Trauma Alerts
(2009-11) at U Texas, Houston
• All had r-TEG
• 53 (2.5%) PEs at median of 6 days (range 2-31 days)
•
Sens. 82%
Spec. 53%
Cotton B, … Holcomb J. J Trauma Acute Care Surg 2012; 72:1470-7
TEG & PE risk assessment
Sens. 49%
Spec. 87%
Cotton B, … Holcomb J. J Trauma Acute Care Surg 2012; 72:1470-7
• Prospective Blinded Cohort Study
• 240 pts undergoing major non-cardiac surgery
• Routinely drew ran TEG 2 hr postop & followed
• 12 thrombotic complications in 10 pts
(6 MI, 2 DVT, 2 PE, 2 CVA)
TEG & Postop Thrombosis
TEG & Postop Thrombosis
TEG & Postop Thrombosis
New Anticoagulant Monitoring
Holcomb JB, et al. Ann Surg 2012; 256:476
TEG & LMWH
• LMWH not typically monitored
• Anti-Xa levels used when needed:
- Limited availability
- Inconsistent data
• TEG Delta R (with & without heparinase) appears to
be a better index of LMWH dose adequacy
White H, et al. Blood Coag & Fibrinolysis 2012; 23:304-10
Van PY, … Schreiber M. J Trauma 2009; 66:1509-17
TEG & LMWH
R < 0.4 associated
with DVT & calls for
LMWH dose
Van PY, … Schreiber M. J Trauma 2009; 66:1509-17
Anti-platelet issues
• Surgical issue: risk of bleeding VS risk of ischemic events
• Medical / Cardiac Issue: variance of response
• Current “Gold Standard” in platelet monitoring is Light
Transmission Platelet Aggregometry (LTA) :
- Requires specialized labs
- Poorly standardized between labs
- Not routinely used clinically
Agarwal S, et al. Anesthesiology 2006; 105:676-83
Conventional TEG & Antiplatelets
• Not helpful
• Kaolin-induced thrombin generation
overshadows any platelet effect
• Lab & clinical experiences have demonstrated
normal TEG MAs in specimens with definitive
platelet inhibition on LTA
Agarwal S, et al. Anesthesiology 2006; 105:676-83
Platelet Mapping
• Modified TEG c Heparin added to prevent
thrombin activity.
• Then add ADP or Arachidonic Acid to
determine the contribution of the ADP &
TxA2 receptors.
• Correlates well with the unwieldy standard
of Light Transmission Aggregometry.
Mylotte D, et al. Cardiovasc Hematolog Agents Med Chem 2011; 9:14-24
Agarwal S, et al. Anesthesiology 2006; 105:676-83
Platelet Mapping
Platelet Mapping
Minimal Platelet Inhibition:
- minimal risk of bleeding
- ischemia risk
Severe Platelet Inhibition:
- risk of bleeding
- minimal ischemia risk
Wohlauer MV, Moore EE, et al. J Am Coll Surg 2012; 214: 739-46
Agarwal S, et al. Anesthesiology 2006; 105:676-83
Platelet Mapping
% Inhibition = 100 - [(MAADP or AA – MAFibrin) / (MAThrombin – MAFibrin) X 100]
>50% Inhibition
30-50% Inhibition
< 30% Inhibition
Response
Partial Response
Lack of Response
Agarwal S, et al. Anesthesiology 2006; 105:676-83
TEG vs LTA vs PFA
65
60
91% Correlation between LTA & TEG
Agarwal S, et al. Anesthesiology 2006; 105:676-83
TEG vs LTA vs PFA
Agarwal S, et al. Anesthesiology 2006; 105:676-83
Preop Antiplatelet Assessment
• Current Anesthesia Policy at U of Wales:
-<
30% Platelet inhibition: proceed with surgery
- > 30% Platelet Inhibition: wait or administer platelets
• “Allows for informed rather than empirical
platelet transfusions.”
Kauer J, et al. British J Anaesthesia; 2009; 103:304-5
Post PCI
J Am Coll Cardiol 2005; 46:1820-6
(n 38)
(n 154)
Post PCI
Gurbel PA, et al. J Am Coll Cardiol 2005; 46:1820-6
Clinical Utility of TEG
• Direct resuscitation of severely injured pts
• Guide anticoagulation therapy
• Guide anti-platelet therapy