Clinical Utility of Thromboelastography

(TEG)

Lowell Chambers, MD
 Secondary Hemostasis (Coagulation Cascade)
CLASSIC COAGULATION CASCADE
INTRINSIC PATH (PTT) EXTRENSIC PATH (PT)
XII XIIa

XI XIa

IX IXa + VIIIa VIIa + TF

X Xa + Va

Ca++
Prothrombin (II) Thrombin (IIa)

Fibrinogen (I) Fibrin (Ia)

 Secondary Hemostasis (Coagulation Cascade)
PHYSIOLOGIC PATHWAY
VIII Platelet
Thrombin
VII + TF

IX IXa + VIIIa*
V
X Xa + Va
XIII (transglutaminase)
II Thrombin
XI XIa
Ca++ XIIIa

Fibrinogen Fibrin Cross-

Linked*
Fibrin
Cell-Based Hemostasis
 Challenges in Coagulation Evaluation

Evaluation of Platelet Function

Monitoring of New generation anticoagulants

Determination of Hyperfibrinolytic States

 Coagulopathy of Trauma
Hyper-
Prot. C Activation
fibrinolysis

ACIDOSIS
Impaired Clotting Factor Function
C
Impaired Platelet Function
O
A
HYPOTHERMIA G
Increased U
CNS Injuries TF Release L
DIC
HIGH ISS O
Long Bone P
Fat Embolism
Fxs A
T
H
Dilution of Clotting Y
Increased
HYPOTENSION Factors & Platelets
IVF & PRBCs

Hess J, Hoyt D, Bouillon B. J Trauma 2008; 65:748-54

 Coagulopathy of Trauma

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

Significant Trauma patients

4x increased mortality

Multifactorial

Currently addressed with:

- Whole Blood Improved
- 1:1:1 Protocols 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.

Potential to save 70-100,000
+
lives annually world-wide
No harm from TXA
+ (NNT1 = 67)
Low Cost (~$6.00/gm)
 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
Hemostatic
status
Stability of clot
 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 & 1960s Dr. Thomas Starzl &
Hypothermic Open Heart Procedures 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 pins 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
Continuous monitoring of
clotting process
Time 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, Achievement Maximum amplitude

first significant of certain clot maximum strength of
clot formation firmness 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 IIa generation Fibrin mesh

Activity Fibrin formation Fibrinplatelet

Hemostatic Coagulation Coag pathways

Component pathways platelets

4-8 min K
Dysfunction
FFP
Hypo- K (min)
R (min) Cryoprecipitate
coagulable (deg)
Hyper- K (min)
R (min)
coagulable (deg)

Copyright 2009 Haemonetics Corp.

 TEG Parameters: MA Maximum amplitude
Maximum clot strength (54 72 mm)
Platelets
Parameter Clot time Clot rate Maximum clot strength

Hemostatic IIa generation Fibrin X-linking

Fibrin formation Fibrinplatelet
Platelet fibrin interactions
Activity
Hemostatic Coagulation Coag pathways Platelets (~80%)
Component pathways platelets Fibrin (~20%)

MA

K
Dysfunction
Hypo- K (min)
R (min)
(deg)
MA
coagulable
ASA
Hyper- K (min)
R (min) MA
coagulable (deg)

Copyright 2009 Haemonetics Corp.

 TEG Parameters: LY30 Lysis at 30 minutes
Clot Breakdown (0 7.5%)

Parameter Clot time Clot rate Maximum clot strength Clot stability

Hemostatic IIa generation Fibrin X-linking

Fibrin formation Fibrinplatelet
Platelet fibrin(ogen) interactions Reduction in clot strength
Activity
Hemostatic Coagulation Coag pathways Platelets (~80%)
Fibrinolysis
Component pathways platelets Fibrin(ogen (~20%)

30 min LY30

MA

R TXA
ACA
EPL

K
Dysfunction
Hypo- K (min) LY30 > 7.5%
R (min)
(deg)
MA EPL > 15%
coagulable
Hyper- K (min)
R (min) MA N/A
coagulable (deg)

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
Hemostatic
status
Stability of clot

Copyright 2009 Haemonetics Corp.

 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-TEG19.2 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 Response

30-50% Inhibition Partial Response
< 30% Inhibition 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